Chronic Stage Of Infection Research Articles

Transcriptome profiling of lumpfish (Cyclopterus lumpus) head kidney to Renibacterium salmoninarum at early and chronic infection stages

Renibacterium salmoninarum causes Bacterial Kidney Disease (BKD) in several fish species. Atlantic lumpfish, a cleaner fish, is susceptible to R. salmoninarum. To profile the transcriptome response of lumpfish to R. salmoninarum at early and chronic infection stages, fish were intraperitoneally injected with either a high dose of R. salmoninarum (1 × 109 cells dose−1) or PBS (control). Head kidney tissue samples were collected at 28- and 98-days post-infection (dpi) for RNA sequencing. Transcriptomic profiling identified 1971 and 139 differentially expressed genes (DEGs) in infected compared with control samples at 28 and 98 dpi, respectively. At 28 dpi, R. salmoninarum-induced genes (n = 434) mainly involved in innate and adaptive immune response-related pathways, whereas R. salmoninarum-suppressed genes (n = 1537) were largely connected to amino acid metabolism and cellular processes. Cell-mediated immunity-related genes showed dysregulation at 98 dpi. Several immune-signalling pathways were dysregulated in response to R. salmoninarum, including apoptosis, alternative complement, JAK-STAT signalling, and MHC-I dependent pathways. In summary, R. salmoninarum causes immune suppression at early infection, whereas lumpfish induce a cell-mediated immune response at chronic infection. This study provides a complete depiction of diverse immune mechanisms dysregulated by R. salmoninarum in lumpfish and opens new avenues to develop immune prophylactic tools to prevent BKD.

Transcriptomic profiling of long non-coding RNAs and messenger RNAs in the liver of mice during Toxoplasma gondii infection

BackgroundToxoplasma gondii is an intracellular protozoan parasite that can infect a wide range of warm-blooded animals, including humans. It poses significant health risks, particularly in immunocompromised individuals and during pregnancy, leading to severe disease manifestations. The liver, being a crucial organ involved in immune response and metabolic regulation, plays a critical role in the host's defense against T. gondii infection.MethodsIn this study, we utilized RNA sequencing to investigate the expression profiles of long non-coding RNAs (lncRNAs) and messenger RNAs (mRNAs) in the liver of mice infected with T. gondii. By employing this method, we obtained a comprehensive overview of the alterations in gene expression occurring in the liver during infection.ResultsBy comparing the infected groups to the control groups, we identified numerous differentially expressed lncRNAs DElncRNAs and DEmRNAs at two stages of infection. Specifically, at the acute infection stage, we found 628 DElncRNAs, and 6346 DEmRNAs. At the chronic infection stage, we identified 385 DElncRNAs and 2513 DEmRNAs. Furthermore, we identified 1959 commonly expressed DEmRNAs, including IL27, Nos2, and Cxcr2, across two infection stages. Enrichment and co-location analyses revealed pathways linked to immune and inflammatory responses during T. gondii infection. Notably, through co-location analysis, our analysis revealed several DElncRNAs, including Gm29156, Gm29157, and Gm28644, which are potentially implicated in the progression of liver inflammation induced by T. gondii. Additionally, functional enrichment analysis disclosed stage-specific characteristics of liver inflammation and immune response, alongside changes in metabolic regulation and immunosuppression pathways.ConclusionsOur findings provide valuable insights into the expression patterns of lncRNAs and mRNAs in the liver at different stages of T. gondii infection. We identified potential regulatory factors and pathways implicated in liver inflammation, thereby enhancing our understanding of the molecular mechanisms underlying liver inflammation and immune responses during T. gondii infection. These findings could contribute to the development of targeted therapeutic strategies for liver inflammation in the context of T. gondii infection.Graphical

Prognostic Significance of Alpha-Fetoprotein in Staging of Chronic Hepatitis B Infection

Background Ascertaining the stage of chronic hepatitis-B infection (CHBI) remains one of the major predicaments to effective therapeutic decision. There is pressing need to forestall dearth of such reliable biomarker(s). Despite the promising tendency of alpha-fetoprotein (AFP), it has not been assessed in staging CHBI.ObjectiveThis study was to determine the prognosis of serum AFP as a biomarker for staging CHBI. MethodsParticipants were grouped into three based on their hepatitis-B envelope antigen (HBeAg) status and alanine aminotransferase (ALT) level. By denoting HbeAg(+) as (EP), HbeAg(-) as (EN), elevated ALT as (H) and normal ALT as (I), the stages were EPH, ENH and ENI. AFP was assayed, One-way ANOVA, Multivariate linear regression and area under curve were adopted for the analysis. ResultsAFP was significantly elevated, (P < 0.05) in EPH, which equally has the highest prevalence of elevated AFP (64.7%). After adjusting for confounding factors, odds ratio was 1.438 (95% CI, 0.62–1.948), while area under the curve for predicting EPH was (0.828, 95% CI, 0.778 –0.895).ConclusionsThe finding of elevated AFP in CHBI is an independent prognostic marker of EPH. It is often associated with necroinflammation; thus, it is a reliable indicator for treatment initiation.Rwanda J Med Health Sci 2023;6(3):355-366

Serum RNase L levels in patients with chronic hepatitis B virus infection.

Chronic hepatitis B virus (HBV) infection still poses a major threat to global health. Oligoadenylate synthetase-ribonuclease L (RNase L) antiviral pathway is one of interferon-induced antiviral effectors. The relationship between RNase L and HBV has never been investigated and we aim to examine the serum RNase L levels in patients with different stages of chronic HBV infection. The patients were enrolled from 1985 to 2000, who had been HBsAg positive for longer than 6months, at the National Taiwan University Hospital. In total, 426 patients with chronic HBV infection were included in this study, including 135 inactive carriers, 148 cirrhosis, and 143 hepatocellular carcinoma (HCC) cases. The RNase L levels increase as the disease severity increases. Higher RNase L levels were associated with higher HBV viral load, and the HBV-RNase L relationship was replaced by the disease severity status when adding disease status into the model. Compared with inactive carriers, the risk of liver cirrhosis was 60-fold (odds ratio=60.8, 95% confidence interval=3.49-1061) with the highest quintile of RNase L levels, after the adjustment of HBV DNA. The dose-response trend was statistically significant with quintiles and one increment of RNase L level in relation to liver cirrhosis. Similar results were found when HCC was compared with inactive carriers, while there was no association when compared between liver cirrhosis and HCC. A positive relationship between serum RNase L and HBV viral titers or advanced disease status is uncovered in this study. Further investigation in this area may provide more details of an innate immune response for HBV and opportunity for novel therapeutic strategy.

Dense granule protein 3 of Toxoplasma gondii plays a crucial role in the capability of the tissue cysts of the parasite to persist in the presence of anti-cyst CD8+ T cells during the chronic stage of infection.

Toxoplasma gondii establishes chronic infection by forming tissue cysts, and this chronic infection is one of the most common parasitic infections in humans. Our recent studies revealed that whereas CD8+ T cells of genetically resistant BALB/c mice have the capability to remove the tissue cysts of the parasite through their perforin-mediated activities, small portions of the cysts are capable of persisting in the presence of the anti-cyst CD8+ T cells. It is currently unknown how those small portions of the cysts resist or escape the T-cell immunity and persist in the hosts. In the present study, we discovered that the cysts, which persisted in the presence of the perforin-mediated CD8+ T-cell immunity, have significantly greater mRNA levels for four dense granule proteins, GRA1, GRA2, GRA3, and GRA7, and one rhoptry protein, ROP35, than the total population of the cysts present in the absence of the T cells. In addition, increased levels of mRNA for GRA1, GRA3, and ROP35 in the cysts significantly correlated with their successful persistence through the condition in which greater degrees of reduction of the cyst burden occurred through anti-cyst CD8+ T cells. In addition, GRA3-deficient T. gondii displayed significantly enhanced elimination of the cysts by anti-cyst CD8+ T cells when compared to the wild-type parasite. These results indicate that GRA3 is a key molecule that mediates in the capability of T. gondii cysts to persist by resisting or evading the anti-cyst activity of CD8+ T cells during the later stage of infection.

Mitochondrial genome amplification of avian haemosporidian parasites from single-infected wildlife samples using a novel nested PCR approach

Haemosporidian parasites that infect birds (Apicomplexa: Haemosporida) are blood parasites that require an invertebrate host (vector) and a vertebrate host for their lifecycle and cause malaria-like diseases. This group of parasites has provided valuable insights into host specificity, virulence, and parasite dispersal. Additionally, they have played a significant role in reshaping our understanding of the evolutionary history of apicomplexans. In order to accurately identify species and to address phylogenetic questions such as the timing of the haemosporidian radiation, the use of a sufficiently large genetic data set is crucial. However, acquiring this genetic data poses significant challenges. In this research, a sensitive nested PCR assay was developed. This assay allows for the easy amplification of complete mitochondrial genomes of haemosporidian parasites in birds, even during the chronic stage of infection. The effectiveness of this new nested PCR assay was evaluated using blood and tissue samples of birds with verified single parasite infections from previous studies. The approach involves amplifying four overlapping fragments of the mitochondrial genome and requires DNA extracts from single-infected samples. This method successfully amplified the complete mitochondrial genomes of 24 distinct haemosporidian parasite lineages found in various bird species. This data is invaluable for conducting phylogenetic analyses and accurately defining species. Furthermore, this study proposes the existence of at least 15 new haemosporidian parasite species based on the genetic information obtained. Data regarding pGRW04, previously categorized as Plasmodium relictum like pSGS1 and pGRW11, indicates that the pGRW04 lineage is actually a separate, hidden Plasmodium species.

Cytokine Gene Expression Profiles during HIV and Helminth Coinfection in Underprivileged Peri-Urban South African Adults.

Intestinal helminth parasites are potent stimulators of T helper type 2 (Th2) and regulatory Th3 anti-inflammatory immune responses, while human immunodeficiency virus (HIV) infections are activators of predominantly T helper type 1(Th1) pro-inflammatory responses. Studies investigating the immune profiles of individuals coinfected with helminths and HIV are scarce. Although it is well known that helminths cause a type 2 immune response during the chronic stage of infection that is characterised by Th2 cell differentiation, eosinophil recruitment, and alternative macrophage activation, the immune mechanisms that regulate tissue damage at the time of parasite invasion are poorly understood. The aim of the study was to determine the cytokine gene expression profiles during HIV and helminth coinfection in underprivileged South African adults living in a peri-urban area with poor sanitary conditions and a lack of clean water supply. Study participants (n = 164) were subdivided into uninfected controls, HIV-infected, helminth-infected, and HIV and helminth-coinfected groups. The Kato-Katz and Mini Parasep techniques and Ascaris lumbricoides-specific Immunoglobulin E (IgE) and Immunoglobulin G4 (IgG4) levels were used to detect helminth infections. Participants' HIV status was determined using two HIV1/2 antibody test kits. RNA was isolated from white blood cells for cytokine (Th1-, Th2-, and Th17-related) and transcription factor gene expression profiling using real-time PCR. Multivariate regression data were adjusted for age, gender, BMI, antiretroviral treatment (ART), and nutritional supplement intake. The HIV and helminth-coinfected group had significantly higher tumour necrosis factor alpha (TNF-α) (adjusted β = 0.53, p = 0.036), interleukin 2 (IL-2) (adjusted β = 6.48, p = 0.008), and interleukin 17 (IL-17) (adjusted β = 1.16, p = 0.001) levels and lower GATA binding protein 3 (GATA3) levels (adjusted β = -0.77, p = 0.018) compared to the uninfected controls. No statistical significance was noted for Th2-related cytokines. The coinfected group had higher proinflammatory Th1- and Th17-related cytokine gene expression profiles compared to the uninfected controls. The findings suggest that pro-inflammatory responses are elevated during coinfection, which supports the hypothesis that helminths have a deleterious effect on HIV immune responses.

Mathematical model analysis of effective intervention strategies on transmission dynamics of hepatitis B virus

Hepatitis B is one of the world’s most common and severe infectious diseases. Worldwide, over 350 million people are currently estimated to be persistent carriers of the hepatitis B virus (HBV), with the death of 1 million people from the chronic stage of HBV infection. In this work, developed a nonlinear mathematical model for the transmission dynamics of HBV. We constructed the mathematical model by considering vaccination, treatment, migration, and screening effects. We calculated both disease-free and endemic equilibrium points for our model. Using the next-generation matrix, an effective reproduction number for the model is calculated. We also proved the asymptotic stability of both local and global asymptotically stability of disease-free and endemic equilibrium points. By calculating the sensitivity indices, the most sensitive parameters that are most likely to affect the disease’s endemicity are identified. From the findings of this work, we recommend vaccination of the entire population and screening all the exposed and migrants. Additionally, early treatment of both the exposed class after screening and the chronically infected class is vital to decreasing the transmission of HBV in the community.

[Transient elastography technology role assessment during the diagnosis and treatment of patients with chronic hepatitis B virus infection].

Objective: To explore the role of transient elastography technology in the assessment of disease staging and treatment in patients with chronic hepatitis B virus (HBV) infection. Methods: Patients who were clinically diagnosed with chronic HBV infection at Beijing Tsinghua Changgung Hospital from January 2018 to December 2021 was collected. Liver stiffness measurement (LSM) examination was performed more than once by transient elastography. The count data were expressed as cases (%) and the χ (2) test was made. Fisher's exact test was used with theoretical frequency less than 5. The measurement data between two groups was compared by t-test. Multiple groups were compared with an analysis of variance. Results: 1 055 patients were included in this study, including 669 (63.4%) males and 386 (36.6%) females. 757 (71.8%) patients were untreated. Among the untreated patients, the LSM value in the immune clearance (10.2 ± 3.8) kPa (187 cases, 40.4%), and the reactivation stages (9.1 ± 3.4) kPa (114 cases, 24.6%) was significantly higher than that in the immune tolerance (8.7 ± 3.6) kPa (78 cases, 16.8%) and immune control stages (8.4 ± 3.5) KPa (84 cases, 18.1%), and the difference between the four groups was statistically significant (F = 5.31 and P = 0.03). With ALT (male: 30 U/L, female: 19 U/L) as defined the normal value, the LSM value in the immune tolerance and the immune control stages were (5.8 ± 0.9) kPa and (7.1 ± 2.5) kPa, respectively, which were significantly lower than those of patients in the immune tolerance and immune control stages, and the difference was statistically significant (P < 0.01). There were 294 (38.8%) patients with uncertain period, excluding patients with fatty liver. Patients with uncertain periods were divided into four gray zone (GZ) groups: immune tolerance stage: LSM (5.1 ± 1.3) kPa was significantly lower than GZ-A (6.5 ± 2.4) kPa, t = 2.06, P = 0.03, and the difference was statistically significant; immune control stage: LSM was (5.6 ± 1.5) kPa, which was also lower than GZ-C (6.8 ± 1.3) kPa, t = 3.08, P = 0.02, and the difference was statistically significant; immune clearance stage: LSM > 8.0 kPa. LSM values showed a year-by-year reduction in patients with expanded indications who started antiviral treatment and were followed up for three years. Conclusion: The LSM value is significantly lower after the decrease of the defined high-normal ALT value in patients with the immune tolerance and immune control stages of chronic HBV infection. The LSM values of GZ-A and GZ-C in the uncertain periods of chronic HBV infection are higher than those of patients in the immune tolerance and immune control stages.

Plasma virome dynamics in chronic hepatitis B virus infected patients.

The virome remains an understudied domain of the human microbiome. The role of commensal viruses on the outcome of infections with known pathogens is not well characterized. In this study we aimed to characterize the longitudinal plasma virome dynamics in chronic hepatitis B virus (HBV) infected patients. Eighty-five longitudinal plasma samples were collected from 12 chronic HBV infected individuals that were classified in the four stages of HBV infection. The virome was characterized with an optimized viral extraction protocol and deep-sequenced on a NextSeq 2500 platform. The plasma virome was primarily composed of members of the Anello- Flavi-, and Hepadnaviridae (HBV) families. The virome structure and dynamics did not correlate with the different stages of chronic HBV infection nor with the administration of antiviral therapy. We observed a higher intrapersonal similarity of viral contigs. Genomic analysis of viruses observed in multiple timepoint demonstrated the presence of a dynamic community. This study comprehensively assessed the blood virome structure in chronic HBV infected individuals and provided insights in the longitudinal development of this viral community.

ASXL1 disruption preserves CD8 T cell exhaustion-progenitor epigenetic programming during chronic stimulation

Abstract Differentiation of CD8 T cells into a terminally exhausted state is a major hurdle limiting efficacy of both immune checkpoint blockade and adoptive cellular immunotherapy approaches. Prior studies describing disruption of the epigenetic regulators DNMT3A and TET2 in CD8 T cells have revealed a critical role of DNA methylation in repressing the proliferative capacity and effector potential of CD8 T cells during exhaustion. Disruption of these genes has also been noted to preserve the proliferative capacity of hematopoietic stem cells (HSCs), resulting in clonal hematopoiesis (CH) and establishing the broader concept that these epigenetic regulators control cellular developmental potential. In addition to DNMT3A and TET2, the histone modifier ASXL1 is a critical regulator controlling CH. Here we report that disruption of ASXL1 in CD8 T cells preserved a stem-like phenotype denoted by increased TCF1 expression, IFN-γ production during chronic infection. At the chronic stage of infection, ASXL1 KO CD8 T cells retained a heightened ability to undergo a proliferative burst during PD-L1 blockade. Genome-wide epigenetic profiling demonstrated that disruption of ASXL1 resulted in inhibition of DNA methylation accompanied by changes in chromatin accessibility. These data document crosstalk between histone modifications and DNA methylation in regulating the transition of stem-like progenitor T cells into terminally exhausted T cells. Collectively, these data demonstrate that ASXL1 is a novel epigenetic regulator controlling development of exhausted CD8 T cells and represents a novel immunotherapeutic target for improving responses to T cell-based cancer immunotherapy.

Programming of checkpoint blockade responsive exhausted T cells by rheostatic IL-2 signals during priming by dendritic cells

Abstract Stem-like progenitor exhausted CD8 T cells are critical for maintaining long-term resistance during chronic infections and cancer, and represent an important checkpoint blockade immunotherapy target for functional reinvigoration and disease control. Here, we show a fate-deterministic role of rheostatic IL-2 signals and differential DC priming in programming the development of stem-like progenitor exhausted CD8 T cells during chronic viral infection. In vivo fate-tracking studies reveal that strong IL-2 signals during priming drive terminal differentiation. In contrast, tempered IL-2 signals are associated with TCF-1 Histem-like precursors, which give rise to progenitor exhausted CD8 T cells, capable of long-term persistence and potent responsiveness to anti-PD-1 therapy in later stages of chronic viral infection. In the context of human tumors as well, single cell RNA-seq analyses of total or antigen-specific tumor infiltrating lymphocytes show an inverse relationship of IL-2 signaling signature with T cell stemness, as well as checkpoint blockade therapy outcomes in melanoma. Our studies further show that the rheostatic control of exhausted T cell fates by differential IL-2 signals is physiologically mediated through differential cell surface expression of IL-2Rα during early stages of T cell activation, which in turn is pioneered during priming by distinct dendritic cell subsets. Notably, moderation of in vivo IL-2 signals during priming promotes the development of stem-like TCF-1 Hilineage, thus supporting a unique strategy for improving clinical immunotherapy outcomes by enhancing the development of long-lived, therapy-responsive stem-like cells with vigorous effector expansion capabilities. Pediatric Cancer Research Foundation to SS, the Rachel Lynn Henley Foundation to VK, the Hopes and Smiles For Children Foundation to VK, In Concert for Cancer Foundation to VK and the National Institutes of Health (CA254168 to TP; CA225517 to PN; AI132819, AI103748 to SS; 5P30CA015704; AI154363 to VK)

Erythrocytic, Enzymatic, and Histological Markers of Oxidative Stress in Subacute and Chronic Stage Infections in Wistar Rats (Rattus norvegicus) Infected with Trypanosoma brucei brucei

Trypanosomiasis is a complex of diseases caused by a haemoprotozoan parasite of medical and veterinary importance. One of the leading factors that cause morbidity and death in trypanosomiasis is oxidative stress. The oxidative stress biomarkers in trypanosomiasis at the subacute and chronic stages of infection were investigated in this study. A total of twenty-four Wistar rats were used; the animals were placed in two groups: group A (subacute and chronic) and group B (control). The weight and body temperature of the experimental animals were determined using a digital weighing balance and thermometer. A hematology analyzer was used to determine the erythrocyte indices. Spectrophotometry was used to estimate enzyme (superoxide dismutase, catalase, and glutathione) activities in the serum, kidney, and liver of experimental animals. Liver, kidney, and spleen were harvested and analyzed for histological changes. The mean body weight of the infected decreased compared to the control (P < 0.05). The mean body temperature of infected individuals increased (35-37°C) compared to the control (P < 0.05). The erythrocyte indices of the infected and control groups indicate a significant decrease (P < 0.05). In erythrocyte indices, only MCHC indicated a nonsignificant decrease (P > 0.05). The SOD of serum shows a significant increase (P < 0.05), and no significant increase SOD (P > 0.05) in kidney and the liver SOD indicates a significant decrease (P < 0.05). The serum, kidney, and liver show a significant increase (P < 0.05) in CAT. The serum GSH from the findings indicates a nonsignificant increase (P > 0.05), and the kidney and liver GSH shows a significant increase (P < 0.05). The correlation analysis for SOD shows nonsignificant negative correlation for serum/kidney, and the serum/liver and kidney/liver show significant positive correlation. The result of CAT shows significant correlations for serum and kidney, serum and liver, and kidney/liver with a positive correlation. The GSH result shows no significant negative correlation for serum/kidney and no significant positive correlation for serum/liver and kidney/liver. The histological damage in the kidney, liver, and spleen was much higher in the chronic stage than in the subacute stage and no tissue damage in the control group. In conclusion, subacute and chronic stage trypanosome infection is associated with changes in hematological indices, antioxidants of the liver, spleen and kidney, and histological architecture.

IL-22-producing CD3 + CD8- T cells increase in immune clearance stage of chronic HBV infection and correlate with the response of Peg-interferon treatment

Interleukin (IL)-22 regulates host defense. This study investigated the predominant IL-22-producing cell subsets under HBV associated immune stages. We found circulating IL-22-producing CD3 + CD8- T cells were significantly increased in immune active (IA) stage than those in immunotolerant stage, inactive carrier and healthy controls (HCs). The plasma IL-22 level was higher in IA and HBeAg-negative CHB compared to HCs. Importantly, CD3 + CD8- T cells were identified as the predominant source of plasma IL-22 production. Up-regulated IL-22-producing CD3 + CD8- T cells obviously correlated with the grade of intrahepatic inflammation. The proportions of IL-22-producing CD3 + CD8- T cells were significantly down-regulated after 48 weeks of Peg-interferon treatment, and the differences were of great significance in patients with normalize ALT levels at 48 weeks, rather than those with elevated ALT levels. In conclusion, IL-22 might play a proinflammatory function in.chronic HBV infected patients with active inflammation and Peg-interferon treatment could attenuate the degree of liver inflammation through down-regulating IL-22-producing CD3 + CD8- T cells.

A necroptosis-independent function of RIPK3 promotes immune dysfunction and prevents control of chronic LCMV infection

Necroptosis is a lytic and inflammatory form of cell death that is highly constrained to mitigate detrimental collateral tissue damage and impaired immunity. These constraints make it difficult to define the relevance of necroptosis in diseases such as chronic and persistent viral infections and within individual organ systems. The role of necroptotic signalling is further complicated because proteins essential to this pathway, such as receptor interacting protein kinase 3 (RIPK3) and mixed lineage kinase domain-like (MLKL), have been implicated in roles outside of necroptotic signalling. We sought to address this issue by individually defining the role of RIPK3 and MLKL in chronic lymphocytic choriomeningitis virus (LCMV) infection. We investigated if necroptosis contributes to the death of LCMV-specific CD8+ T cells or virally infected target cells during infection. We provide evidence showing that necroptosis was redundant in the pathogenesis of acute forms of LCMV (Armstrong strain) and the early stages of chronic (Docile strain) LCMV infection in vivo. The number of immune cells, their specificity and reactivity towards viral antigens and viral loads are not altered in the absence of either MLKL or RIPK3 during acute and during the early stages of chronic LCMV infection. However, we identified that RIPK3 promotes immune dysfunction and prevents control of infection at later stages of chronic LCMV disease. This was not phenocopied by the loss of MLKL indicating that the phenotype was driven by a necroptosis-independent function of RIPK3. We provide evidence that RIPK3 signaling evoked a dysregulated type 1 interferone response which we linked to an impaired antiviral immune response and abrogated clearance of chronic LCMV infection.

Whole blood transcriptome profiles of trypanotolerant and trypanosusceptible cattle highlight a differential modulation of metabolism and immune response during infection by Trypanosoma congolense

Animal African trypanosomosis, caused by blood protozoan parasites transmitted mainly by tsetse flies, represents a major constraint for millions of cattle in sub-Saharan Africa. Exposed cattle include trypanosusceptible indicine breeds, severely affected by the disease, and West African taurine breeds called trypanotolerant owing to their ability to control parasite development, survive and grow in enzootic areas. Until now the genetic basis of trypanotolerance remains unclear. Here, to improve knowledge of the biological processes involved in trypanotolerance versus trypanosusceptibility, we identified bovine genes differentially expressed in five West African cattle breeds during an experimental infection by Trypanosoma congolense and their biological functions. To this end, whole blood genome-wide transcriptome of three trypanotolerant taurine breeds (N’Dama, Lagune and Baoulé), one susceptible zebu (Zebu Fulani) and one African taurine x zebu admixed breed (Borgou) were profiled by RNA sequencing at four time points, one before and three during infection. As expected, infection had a major impact on cattle blood transcriptome regardless of the breed. The functional analysis of differentially expressed genes over time in each breed confirmed an early activation of the innate immune response, followed by an activation of the humoral response and an inhibition of T cell functions at the chronic stage of infection. More importantly, we highlighted overlooked features, such as a strong disturbance in host metabolism and cellular energy production that differentiates trypanotolerant and trypanosusceptible breeds. N’Dama breed showed the earliest regulation of immune response, associated with a strong activation of cellular energy production, also observed in Lagune, and to a lesser extent in Baoulé. Susceptible Zebu Fulani breed differed from other breeds by the strongest modification in lipid metabolism regulation. Overall, this study provides a better understanding of the biological mechanisms at work during infection, especially concerning the interplay between immunity and metabolism that seems differentially regulated depending on the cattle breeds.

Substantial relation between the bacterial biofilm and oncogenesis progression in host.

Globally, bacteria are well-known microorganisms for bacterial biofilm infection. Bacterial biofilm has generated antibiotic resistance and led the persistent infection. But new complications arise with a biofilm that bacterial biofilm shows the new association with oncogenesis. Some bacteria have a carcinogenic nature at the chronic infection stage like Salmonella Typhi, Helicobacter pylori. Thus, biofilm has a significant role in oncogenesis. Few pieces of evidence also support that the bacterial biofilm has a potential role to develop oncogenesis in the human body. Bacterial biofilm is responsible to induce chronic inflammation and is the main basis for the oncogenesis process. But bacterial biofilm association with the oncogenesis mechanism is unknown yet. This article focuses on the function of bacterial biofilm in tumor formation and the mechanism that encourages the oncogenesis and provide a possible and interesting hypothesis involved in between biofilm and host oncogenesis progression. The discussed relationship will provide a sound direction in the field of oncology and concept may give an informative direction in diagnosis and treatment. Bacterial biofilm behavior could be significantly linked with cancer cell formation. This article attracts the attention of researchers of the field because biofilm mediated oncogenesis further indicate towards an important issue in human health.

Articles of Significant Interest in This Issue.

Helicobacter pylori establishes chronic human stomach infections characterized by persistent inflammation. Previous work had identified a high-inflammation H. pylori mutant lacking the chemoreceptor TlpA. To understand H. pylori inflammation control, Johnson et al. (e00322-22) compared colonization dynamics and host response between the tlpA mutant and the wild type. Both strains caused inflammation at the late, chronic-infection stages, but surprisingly this inflammation fluctuated temporally and was offset in period between the wild type and the tlpA mutant. tlpA mutants also showed high early-infection bacterial numbers. These results suggest that chronic inflammation is more dynamic than previously thought and may be influenced by colonization properties of early infection.

Identification of Molecular Mechanisms Involved in Viral Infection Progression Based on Text Mining: Case Study for HIV Infection.

Viruses cause various infections that may affect human lifestyle for durations ranging from several days to for many years. Although preventative and therapeutic remedies are available for many viruses, they may still have a profound impact on human life. The human immunodeficiency virus type 1 is the most common cause of HIV infection, which represents one of the most dangerous and complex diseases since it affects the immune system and causes its disruption, leading to secondary complications and negatively influencing health-related quality of life. While highly active antiretroviral therapy may decrease the viral load and the velocity of HIV infection progression, some individual peculiarities may affect viral load control or the progression of T-cell malfunction induced by HIV. Our study is aimed at the text-based identification of molecular mechanisms that may be involved in viral infection progression, using HIV as a case study. Specifically, we identified human proteins and genes which commonly occurred, overexpressed or underexpressed, in the collections of publications relevant to (i) HIV infection progression and (ii) acute and chronic stages of HIV infection. Then, we considered biological processes that are controlled by the identified protein and genes. We verified the impact of the identified molecules in the associated clinical study.

Review on Schistosomiasis: Epidemiology and Clinical Manifestation up to Date

Schistosomiasis is a parasite disease that affects both humans and animals and is brought on by the blood flukes of the genus Schistosoma. It is one of the world’s most enduring neglected tropical diseases. Sub-Saharians make up more than 90% of them, and a significant portion of Ethiopians are afflicted and at risk. It spread across the entire nation and was correlated with the rapid development of water resources and population growth. The two species of freshwater snails, Biomphalaria pfeifferi and Biomphalaria sudanica, are responsible for the parasite’s transmission in Ethiopia. Compared to the three primary schistosomes that infect people, Schistosoma mansoni, Schistosoma haematobium, Schistosoma japonicum, Schistosoma intercalatum, and Schistosoma mekongi have less of an epidemiological impact. Geographically, S. haematobium and S. mansoni are more common in Africa than other species. Epidemiological coverage is also influenced by seasonal distributions throughout the postrainy season, as well as the cold and dry seasons. The organs and systems implicated in its pathogenic dissemination include the intestines, urogenital systems, the pulmonary system, the liver, spleen, and the brain. Ecological change and sociocultural influences are risk factors for water contamination. Regarding clinical symptoms, the penetration of cercariae into the dermis, cercarial dermatitis, acute schistosomiasis, and the chronic stage of infection are significant. Mammals and snails serve as the two hosts for the schistosome life cycle. It can be diagnosed through clinical exams and laboratory techniques. Praziquantel can be used to treat this condition, and it can be prevented by taking precautions during ecological shifts that may result in epidemics. Other measures to take include providing clean water, maintaining good hygiene, controlling mosquitoes, and spreading health awareness.