Chronic Persistent Infection Research Articles

Disease Tolerance and Pathogen Resistance Genes May Underlie Trypanosoma cruzi Persistence and Differential Progression to Chagas Disease Cardiomyopathy.

Chagas disease is caused by infection with the protozoan Trypanosoma cruzi and affects over 8 million people worldwide. In spite of a powerful innate and adaptive immune response in acute infection, the parasite evades eradication, leading to a chronic persistent infection with low parasitism. Chronically infected subjects display differential patterns of disease progression. While 30% develop chronic Chagas disease cardiomyopathy (CCC)—a severe inflammatory dilated cardiomyopathy—decades after infection, 60% of the patients remain disease-free, in the asymptomatic/indeterminate (ASY) form, and 10% develop gastrointestinal disease. Infection of genetically deficient mice provided a map of genes relevant for resistance to T. cruzi infection, leading to the identification of multiple genes linked to survival to infection. These include pathogen resistance genes (PRG) needed for intracellular parasite destruction, and genes involved in disease tolerance (protection against tissue damage and acute phase death—DTG). All identified DTGs were found to directly or indirectly inhibit IFN-γ production or Th1 differentiation. We hypothesize that the absolute need for DTG to control potentially lethal IFN-γ PRG activity leads to T. cruzi persistence and establishment of chronic infection. IFN-γ production is higher in CCC than ASY patients, and is the most highly expressed cytokine in CCC hearts. Key DTGs that downmodulate IFN-γ, like IL-10, and Ebi3/IL27p28, are higher in ASY patients. Polymorphisms in PRG and DTG are associated with differential disease progression. We thus hypothesize that ASY patients are disease tolerant, while an imbalance of DTG and IFN-γ PRG activity leads to the inflammatory heart damage of CCC.

Infection-Induced Kidney Diseases.

Infection induced kidney diseases are of concern for clinicians because timely detection and treatment of infections may cure or limit the extent of injury inflicted by microorganisms causing the infections. Infections can cause kidney injury by either direct invasion, or indirectly by immune mediated mechanisms, which manifest as post-infectious glomerulonephritis, or infection-related glomerulonephritis. Clinical manifestations may be acute or chronic depending on the microorganisms, endemic/epidemic nature and source of infection. All microbials virus, bacteria, mycobacteria, fungus, and protozoa have been implicated in kidney diseases either causing direct kidney injuries or immune-mediated injuries. Infection control practices in large parts of world is limited by poverty, social behavior, high population density, deforestation, inadequate access to safe drinking water, and poor health care facilities. Although, antimicrobials and vaccinations have successfully eradicated and cured many infectious diseases; however injudicious antimicrobial use and emergence of resistant organisms complicated the disease severity like secondary renal amyloidosis with chronic persistent infection. Re-emergence of various infections has been a recent pattern in developed world leading to uncertain diagnostic challenges, and association with kidney diseases.

Functional Annotation and Analysis of Dual Oxidase 1 (DUOX1): a Potential Anti-pyocyanin Immune Component.

Dual Oxidase 1 (DUOX1) is a prominent immune system component primarily expressed in esophagus, lungs, skin, and urinary bladder including others. DUOX1 is involved in lactoperoxidase-mediated innate immunity at mucosal surfaces by generation of antimicrobial hypothiocyanite at the apical surface of epithelial lining. Upon detection of bacterial pathogens mainly Pseudomonas aeruginosa, DUOX1 is activated in bronchial epithelial cells. Both the host and pathogen enter a redox dual with DUOX1 and hypothiocyanite from host and Pyocyanin (PCN) as a redox active virulence factor from P. aeruginosa. The synergy of the both enzymes permanently oxidizes PCN and thus holds the potential to prevent PCN-induced virulence, which otherwise paves the way for establishment of persistent chronic infection. In this study, we structurally and functionally annotated the DUOX1, predicted its 3d structure, physio-chemical properties, post-translational modifications, and genetic polymorphism analysis with subsequent disease-associated single-nucleotide variations and their impact on DUOX1 functionality by employing in silico approaches. DUOX1 holds greater homology with gorilla and chimpanzee than other primates. The localization signal peptide was present at the beginning of the peptide with cleavage site at 22 aa position. Three distinct functional domains were observed based on homology: An_peroxidase, FRQ1, and oxido-reductase domains. Polymorphism analysis revealed > 60 SNPs associated with different cancers with probable damaging effects. No cancer-associated methylated island was observed for DUOX1. Three-dimensional structure was developed via homology modeling strategy. The proper annotation will help in characterization of DUOX1 and enhance our knowledge of its functionality and biological roles.

First Detection of Chlamydia trachomatis 'Swedish' Variant (nvCT) in a Russian Couple with Infertility.

Background:Chronic asymptomatic chlamydial genital infection caused by the wild-type of Chlamydia trachomatis (wtCT) is the most common bacterial infection causing human infertility. The novel ‘Swedish’ variant of С.trachomatis (nvCT) which contains a 377 bp deletion in a region that is specifically targeted in some nucleic acid amplification tests may impede diagnosis.Objective: The study aimed to investigate whether nvCT may be a possible cause of infertility in a couple undergoing in vitro fertilization (IVF).Method:Clinical specimens from both genital (urethra and cervix) and extra-genital sites (pharynx, conjunctive, blood) of a couple who experienced multiple unsuccessful attempts at pregnancy by natural fertilization and IVF procedures were analyzed before and after antibiotic therapy. Both partners had neither somatic nor endocrinal abnormality nor any clinically apparent genital manifestations of Chlamydia or other STIs.Results:Before antibiotic therapy all the samples of the Female Partner (FP) contained DNA of only the nvCT. After antibiotic therapy, additionally, DNA of wtCT of genovars E and D was detected in specimens from her conjunctiva and oropharynx. All samples of the Male Partner (MP) revealed co-infection of nvCT and wtCT. Identical SNP within the variable region 4 (VD4) of the ompA gene confirmed the identity of the wtCT strains found in both partners. The FP had a positive anti-chlamydial IgG titer. The sperm characteristics of the MP, motility (immotile spermatozoa was 51.1% versus 21.6%) and vitality (46% versus 68%) declined progressively, and the MP anti-chlamydial IgG titer was negative.Conclusion:Infertility in this couple may have been caused by chronic asymptomatic and persistent nvCT-associated infection that was complicated by re-infection later with wtCT. This study illustrates the importance of including detection methods for nvCT strains in the investigation of infertility cases.

PRELIMINARY RESULTS OF EVALUATION OF MICROBIOCENOSIS OF THE MUCOUS MEMBRANES OF THE VAGINA, CERVICAL CANAL AND UTERINE CAVITY IN WOMEN OF REPRODUCTIVE AGE WITH POLYPS OF THE ENDOMETRIUM

Endometrial polyps are benign neoplasms arising in the uterine cavity. The exact causes of the appearance of endometrial polyps are unknown. Recently, in the literature there are data on the factors predisposing to the development of the disease, which include, the chronic inflammatory process in the female genital organs.The purpose of the study was to evaluate the microbiocenosis of the vagina, cervical canal and uterine cavity in women of reproductive age with polyposis of the endometrium.Material and methods of investigation. Thirty women of reproductive age were examined, of which 15 women with endometrial polyps (the main study group) and 15 gynecologically healthy women (control group). All examined general clinical methods of research, ultrasound, hysteroscopy, as well as bacterioscopic and bacteriological studies, ELISA and PCR contents of the vagina and cervical canal cervix, aspirate the uterine cavity.Results of the study and their discussion. In the main group, the normocoenosis of the vagina is defined only in 3 (20%) women, the intermediate type in 4 (26.7%) cases, dysbiosis in 5 (33.3%) women, colpitis caused by fungi of the genus Candida spp. - in 2 (13,3%) patients and trichomonadi colpitis - in 1 (6,6%) patients of the main survey group. With vaginal dysbiosis, a high content of anaerobic microorganisms is established. The examination of the microflora of the cervical canal by PCR method and also by bacteriological culture showed that 12 (80,0%) patients with endometrial polyposis had a wide spectrum of viral-bacterial associations of microorganisms, with the most frequently determined 2-3 component combination of them. The study of contamination of the uterine cavity showed that of the total number of patients in 6 (40,0%) the presence of a viral and/or bacterial agent was detected.Conclusions. The conducted study showed that in 53,3% of patients with endometrial polyps there is a chronic inflammatory process of the uterine mucosa, against a background of disturbance of the state of the microflora of both the vagina and the cervix in 80% of the examined. The presence of chronic persistent infection can have an effect on the development of morpho-functional changes and hyperproliferative processes of the endometrium.

Toll-like receptors-mediated innate immune responses in HBV infection

Hepatitis B virus (HBV) infection is still a major health problem worldwide, but the immunological mechanisms by which HBV causes chronic persistent infection remains controversial. HBV has evolved a series of strategies to interfere TLRs-mediated innate immunity in response to the host immune system and the dysfunction of TLRs is an important cause of persistent virus infection. The innate immune system is activated by pathogens recognition receptors (PRRs) that recognize specific pathogen associated molecular? patterns (PAMPs). Toll-like receptors (TLRs) are important PRRs and play a vital role in mediating innate immune responses to HBV, which is associated with the early clearance of HBV and the subsequent activation of specific immune responses. This review focused on the interplay between HBV and TLRs-mediated innate immune responses as well as research findings about immune therapeutic strategies established based on TLRs. Key words: Toll-like receptors (TLRs); Hepatitis B virus (HBV); Innate immunity

Prospects in Innate Immune Responses as Potential Control Strategies against Non-Primate Lentiviruses.

Lentiviruses are infectious agents of a number of animal species, including sheep, goats, horses, monkeys, cows, and cats, in addition to humans. As in the human case, the host immune response fails to control the establishment of chronic persistent infection that finally leads to a specific disease development. Despite intensive research on the development of lentivirus vaccines, it is still not clear which immune responses can protect against infection. Viral mutations resulting in escape from T-cell or antibody-mediated responses are the basis of the immune failure to control the infection. The innate immune response provides the first line of defense against viral infections in an antigen-independent manner. Antiviral innate responses are conducted by dendritic cells, macrophages, and natural killer cells, often targeted by lentiviruses, and intrinsic antiviral mechanisms exerted by all cells. Intrinsic responses depend on the recognition of the viral pathogen-associated molecular patterns (PAMPs) by pathogen recognition receptors (PRRs), and the signaling cascades leading to an antiviral state by inducing the expression of antiviral proteins, including restriction factors. This review describes the latest advances on innate immunity related to the infection by animal lentiviruses, centered on small ruminant lentiviruses (SRLV), equine infectious anemia virus (EIAV), and feline (FIV) and bovine immunodeficiency viruses (BIV), specifically focusing on the antiviral role of the major restriction factors described thus far.

Novel Glycopolymer Eradicates Antibiotic- and CCCP-Induced Persister Cells in Pseudomonas aeruginosa.

Antibiotic treatments often fail to completely eradicate a bacterial infection, leaving behind an antibiotic-tolerant subpopulation of intact bacterial cells called persisters. Persisters are considered a major cause for treatment failure and are thought to greatly contribute to the recalcitrance of chronic infections. Pseudomonas aeruginosa infections are commonly associated with elevated levels of drug-tolerant persister cells, posing a serious threat to human health. This study represents the first time a novel large molecule polycationic glycopolymer, poly (acetyl, arginyl) glucosamine (PAAG), has been evaluated against antibiotic and carbonyl cyanide m-chlorophenylhydrazone induced P. aeruginosa persisters. PAAG eliminated eliminated persisters at concentrations that show no significant cytotoxicity on human lung epithelial cells. PAAG demonstrated rapid bactericidal activity against both forms of induced P. aeruginosa persister cells resulting in complete eradication of the in vitro persister cells within 24 h of treatment. PAAG demonstrated greater efficacy against persisters in vitro than antibiotics currently being used to treat persistent chronic infections such as tobramycin, colistin, azithromycin, aztreonam, and clarithromycin. PAAG caused rapid permeabilization of the cell membrane and caused significant membrane depolarization in persister cells. PAAG efficacy against these bacterial subpopulations suggests it may have substantial therapeutic potential for eliminating recurrent P. aeruginosa infections.

Benzo(a)pyrene attenuates the pattern-recognition-receptor induced proinflammatory phenotype of murine macrophages by inducing IL-10 expression in an aryl hydrocarbon receptor-dependent manner

Polycyclic aromatic hydrocarbons such as benzo(a)pyrene (BaP) are environmental contaminants known to be immunosuppressive. Most effects of BaP towards immune cells are thought to be mediated through activation of the aryl hydrocarbon receptor (AhR). The AhR is a ligand-activated transcription factor, which plays a critical modulatory role in various cells during immune response. Macrophages are key players in innate immunity against intracellular bacteria and are discussed to be a target of AhR-mediated immune regulation. However, so far there is only incomplete knowledge about the effects of BaP on activated macrophages and whether these effects are AhR-dependent in each case. Using murine bone marrow-derived macrophages (BMMs) stimulated with heat-killed salmonellae as a source of different pathogen-associated molecular patterns (PAMPs) for stimulation of different pattern recognition receptors (PRRs) as an in-vitro model, we studied the immunomodulatory effects of low-dose BaP exposure. PRR-activated BMMs produced nitric oxide (NO) and a spectrum of proinflammatory cytokines, i.e. tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and IL-12 but also the anti-inflammatory cytokine IL-10. While BaP exposure suppressed the production of proinflammatory cytokines, the secretion of IL-10 was augmented. Moreover, BaP exposure increased the expression of major histocompatibility complex class II (MHC-II), CD14, Fcγ receptor I (FcγRI/CD64), or CD86, enhanced NO production and phagocytosis what may be beneficial for phagocytosis and killing of microbial pathogens. Of note, without PRR activation low-dose BaP exposure has little influence on the macrophage phenotype. BMMs from AhR-deficient (Ahr−/−) mice were widely refractory to BaP-induced modulation of cytokine production, surface marker expression, and functional properties in response to PAMPs stimulation, indicating that these effects are dependent on AhR. In summary, these data suggest that induction of AhR-mediated signalling pathways by BaP may attenuate the proinflammatory phenotype of PRR-activated BMMs, while activating IL-10-mediated anti-inflammatory properties but also enhancing uptake and killing of pathogens as well as antigen presentation. Together these features imply a favourable role of BaP exposure for macrophage functions in an ongoing immune response. However, the strong induction of IL-10 may lead to defective pathogen clearance and subsequently to chronic persistent infection. This concept suggests an inhibitory rather than a supporting influence of environmental BaP on immunity to infection or cancer and also emphasises the important regulatory role of AhR in immunity and inflammation.

CORRELATION BETWEEN ENROVIRUS INFECTION AND ACUTE STROKE ON THE GROUND OF VIROLOGICAL, MOLECULAR GENETIC AND SEROLOGICAL METHODS OF DIAGNOSIS

Relevance. Numerous virological studies prove the importance of enteroviruses in human somatic pathology. However, the etiopathogenetic role of enterovirus infection in patients with acute cerebrovascular disorder (GVMK) is not sufficiently highlighted.
 Objective: to establish the value of enterovirus infection as a trigger factor in the pathogenesis of acute stroke.
 Materials and methods. The pear blood serum of 72 patients with acute stroke (main group) and 35 patients with neurological pathology without vascular pathology (group of comparison) were screened for presence of enteroviruses using the virological method, detection of enterovirus genomes using a polymerase chain reaction and the presence of specific Ig M and Ig G to enteroviruses in the enzyme-linked immunosorbent assay (ELISA).
 Results. The enterovirus genomes were isolated from blood serum in 23,6±5,9 % of patients with acute stroke, that is significantly higher than in patients of the comparison group – 2,9±2,8 % (p <0,05). The enteroviruses were isolated in 11 cases of 17 PCR-positive blood serum samples of the main group. These viruses were identified as Coxsackie B viruses (serotypes 2, 3, 4) and ECHO viruses (serotypes 6, 9, 27 (two strains), 29), three strains of viruses could not be identified. The presence of specific Ig M and Ig G in blood serum of 4 patients with HPMC, as well as enterovirus genomes, has been established. It suggest that they have a recent enterovirus infection, or can indicate a recent enterovirus infection or exacerbation of chronic enterovirus infection. Only specific Ig G in the absence of Ig M were detected in blood serum of 4 PCR positive patients, that can indicate chronic enterovirus infection. Only Ig M in the absence of Ig G was detected in blood serum of 6 PCR-positive patients, that can indicate acute enterovirus infection. No Ig M or Ig G in serum from three PCR-positive patients were detected, possibly due to the presence of latent enterovirus infection.
 Conclusions. Acute and chronic persistent enterovirus infection plays a possible trigger role in the development of acute stroke.
 The combination of PCR to detect genomes of enteroviruses, virological for the isolation and identification of viruses, and ELISA for the detection of specific Ig M and Ig G to enteroviruses should be recommended for the diagnosis of persistent enterovirus infection in patients with acute stroke.

Thermostable xylanase inhibits and disassembles Pseudomonas aeruginosa biofilms

Pseudomonas aeruginosa biofilms are problematic and play a critical role in the persistence of chronic infections because of their ability to tolerate antimicrobial agents. In this study, various cell-wall degrading enzymes were investigated for their ability to inhibit biofilm formation of two P. aeruginosa strains, PAO1 and PA14. Xylanase markedly inhibited and detached P. aeruginosa biofilms without affecting planktonic growth. Xylanase treatment broke down extracellular polymeric substances and decreased the viscosity of P. aeruginosa strains. However, xylanase treatment did not change the production of pyochelin, pyocyanin, pyoverdine, the Pseudomonas quinolone signal, or rhamnolipid. In addition, the anti-biofilm activity of xylanase was thermally stable for > 100 days at 45°C. Also, xylanase showed anti-biofilm activity against one methicillin-resistance Staphylococcus aureus and two Escherichia coli strains.

Etiopathogenetic rationale usage of treatment-and-prophylactic complex in patients suffering from chronic herpetic infection, who need dental implantation

The purpose of this work - evaluation of clinical efficacy of treatment-and-prophylactic complex in patients with chronic herpetic infection who need dental implantation.Materials and methods. A group of patients consisted from 35 people with persistent chronic herpes infection who need dental implantation was examined in dynamics of treatment-and-prophylactic complex using (Amyksyn®ІC drug for prevention scheme (according to the manual) before implants placement and the preparation with antioxidant activity Quertulin according to the scheme of treatment postoperatively).Results. Patients in the main group demonstrated a decrease in the inflammatory process activity and the local immune response improvement. On the 7th day after implantation the activity of catalase increased by 32.1% compared to the initial indices, on the 21st day after the implantation - it reached the level of the control group. Elastase activity decreased on the 7th day in 2.4 times, on the 21st day – in 7.1 times as much as compared to the rate before the start of the complex usage. Lysozyme activity decreased on the 7th day by 60.3%, on the 21st day — in 2 times. Urease activity decreased on the 7th day by 47.9%, on the 21st day - by 77.1% and reached the level of the control group. The level of malonic dialdehyde decreased on the 7th day by 40.0%, on the 21st day - by 63.1% as compared with the control. AP-index reached the level of the control group by the 21st day after implantation. Glycoproteins and sialic acids levels decreased as compared to the rate before the use already on the 7th day by 21.9 and 21.0% respectively; on the 21st day the parameters reached the level of the control group. The content of IL-1 and IL-6 are significantly reduced on the 7th day by 52.9 and 29.0%, on the 21st day - by 62.2 and 31.8% as compared to the control group. IL-4 level increased on the 7th day of treatment by 23.2% and by 60.7% - on the 21st day after implantation.Conclusions. The dynamics of oral liquid biochemical parameters of people with persistent chronic herpes infection during dental implantation indicates proper efficiency of the treatment and prophylactic complex. Positive changes can be explained by synergy effects of drugs, which are able to significantly reduce inflammatory markers and the level of enzyme activity, which reflect the degree of bacterial contamination and antioxidant status of oral fluid, and are able to increase the activity of non-specific immune and antioxidant protection.

Detection of Mycobacterium avium subsp. paratuberculosis (MAP) in Faeces of Buffaloes (Bubalus bubalis) from Malwa Region of Madhya Pradesh

In ruminant, Mycobacterium avium subsp. paratuberculosis (MAP) causes chronic persistent infection in small and large intestine, resulting in chronic persistent diarrhea. It is also known as paratuberculosis (JD). It is increasingly being recognized as a problem that adversely affects animal health leading to significant economic losses to livestock industry. Recent emerging evidences have established a link between MAP and inflammatory bowel disease (IBD), Crohn’s disease (CD) suggesting its Zoonotic importance hence the present study was designed to find out percent incidence of MAP infection in buffaloes from Malwa region of Madhya Pradeh by using faecal microscopy. The study was conducted in buffaloes (females and males), belonging to different region of Malwa tract viz. Depalpur, Dewas, Mhow, Dhar (Sundrel), Indore and Maheshwar ranging between 1 to 10 years of age, slaughtered at Cantonment Board slaughter house, Mhow and Nagar Nigam Indore. Based on the presence of pink coloured short rod (0.5-1.5 micron) shaped MAP bacteria by feacal smear examination revealed 79.33% (119/150) incidence of MAP in buffaloes of Malwa region.

Alpha-enolase regulates hepatitis B virus replication through suppression of the interferon signalling pathway.

Persistent chronic infection with hepatitis B virus (HBV) is a major risk factor for the development of HBV-related diseases. The molecular mechanisms that underlie HBV infection and associated carcinogenesis are not fully understood. The aim of this study was to explore the role of ENO1 in HBV replication processes. Here, we examined ENO1 expression levels in HBV-infected and non-HBV-infected liver tissues and cells by Western blot analysis, real-time PCR and immunohistochemistry. In addition, HBsAg and HBeAg in the media of transfected HepG2.2.15 cells were detected using an electrochemical luminescence analyser within 48hours after ENO1-specific siRNA transfection. The expression levels of HBV DNA, type I interferon and 5 downstream IFN-stimulated genes in HepG2.2.15 cells were examined using real-time PCR. We found ENO1 expression was upregulated in the HBV-infected liver tissues and cells. Silencing of ENO1 resulted in a significant reduction in HBV replication, and this siRNA-mediated reaction also caused the upregulation of expression of type I interferon and downstream IFN-stimulated genes. Therefore, we come to the conclusion ENO1 is involved in HBV replication. It is therefore likely that HBV replication is enhanced following suppression of the IFN signalling pathway. However, the mechanisms that underpin ENO1-mediated modulation of the IFN signalling pathway remain to be elucidated.

Immune checkpoint blockade in infectious diseases.

The upregulation of immune checkpoint molecules, such as programmed cell death protein 1 (PD1) and cytotoxic T lymphocyte antigen 4 (CTLA4), on immune cells occurs during acute infections, such as malaria, as well as during chronic persistent viral infections, including HIV and hepatitis B virus. These pathways are important for preventing immune-driven pathology but can also limit immune-mediated clearance of the infection. The recent success of immune checkpoint blockade in cancer therapy suggests that targeting these pathways would also be effective for preventing and treating a range of infectious diseases. Here, we review our current understanding of immune checkpoint pathways in the pathogenesis of infectious diseases and discuss the potential for therapeutically targeting these pathways in this setting.

Regulatory NK cells mediated between immunosuppressive monocytes and dysfunctional T cells in chronic HBV infection

Background and aimsHBV infection represents a major health problem worldwide, but the immunological mechanisms by which HBV causes chronic persistent infection remain only partly understood. Recently, cell subsets with suppressive...

Association of single nucleotide polymorphisms in microRNAs with susceptibility to hepatitis B virus infection and HBV-related liver complications: A study in a Saudi Arabian population.

The aim of this study was to evaluate the association of 10 SNPs in different microRNAs (miRNAs) with susceptibility to hepatitis B virus (HBV) infection, HBV clearance, persistence of chronic HBV infection, and progression to liver cirrhosis and hepatocellular carcinoma (HCC). Patients were categorized into the following groups: inactive HBV carrier, active HBV carrier, HBV-cleared subject and cirrhosis+HCC. Samples were analysed for 10 SNPs in microRNAs using either PCR-based genotyping or the TaqMan assay. We found that rs1358379 was associated with susceptibility to HBV infection, HBV clearance, persistent chronic HBV infection and liver cirrhosis+HCC. In addition, we found that rs2292832 and rs11614913 were associated with risk of HBV infection, viral clearance and cirrhosis+HCC, whereas rs2910164 was associated with proneness to HBV infection, and ability to clear the virus. There was evidence of associations between rs6505162 and HBV clearance and the development of liver disease, whereas a single association was found between rs2289030 and HBV clearance. Similarly, rs7372209 and rs4919510 were specifically associated with the development of HBV-induced liver complications. SNPs in miRNAs affect the susceptibility, clearance and progression of HBV infection in Saudi Arabian patients. We found, using Gene Ontology or pathway analyses, that these genes may contribute to the pathophysiology of HBV infection and related liver complications. However, differences in the association of examined SNPs with various clinical stages indicate variations in the respective functional roles of these polymorphisms and their miRNAs, and thus, further investigation to fully explore their therapeutic potential is warranted.

Infection-adapted emergency hematopoiesis promotes visceral leishmaniasis.

Cells of the immune system are derived from hematopoietic stem cells (HSCs) residing in the bone marrow. HSCs become activated in response to stress, such as acute infections, which adapt the bone marrow output to the needs of the immune response. However, the impact of infection-adapted HSC activation and differentiation on the persistence of chronic infections is poorly understood. We have examined here the bone marrow outcome of chronic visceral leishmaniasis and show that the parasite Leishmania donovani induces HSC expansion and skews their differentiation towards non-classical myeloid progenitors with a regulatory phenotype. Our results further suggest that emergency hematopoiesis contributes to the pathogenesis of visceral leishmaniasis, as decreased HSC expansion results in a lower parasite burden. Conversely, monocytes derived in the presence of soluble factors from the infected bone marrow environment are more permissive to infection by Leishmania. Our results demonstrate that L. donovani is able to subvert host bone marrow emergency responses to facilitate parasite persistence, and put forward hematopoiesis as a novel therapeutic target in chronic infections.

Biofilm production by uropathogens causing catheter associated urinary tract infection

Background: The microbial populations within urinary catheter frequently develop as biofilms, directly attaching to the surface of catheters. Bacteria in biofilm are protected from antimicrobial chemotherapy as well as host defence mechanisms, establishing chronic persistent infections, septicemia and death if not treated. Material and Method: The present study, includes 200 patients, catheterized for >48 hours at CIMS, Bilaspur. Urine samples were collected and inoculated in nutrient agar, blood agar and MacConkey agar plates and identification done as per standard procedure. This study was conducted to detect biofilm formation ability of uropathogens by two different methods (Tube and Congo red agar method) and compare their antibiotic sensitivity by using Kirby-Bauer disc diffusion method. Results: Out of 200 urine samples significant bacteriuria were detected in 148(74%) of samples and no growth found in 52(26%) samples and 14 samples showed growth of 2 microorganisms. A total no. of 162 microorganisms were isolated from 200 urine samples. Among these 162 isolates E. Coli was 29.62%, Pseudomonas aeruginosa 11.72%, Klebsiella sp 18.51%, Citrobactor sp 7.40%, Staphylococcus aureus 3.08%, and Coagulase negative Staphylococci 11%. Among these 162 isolates, a total of 91(56.17%) isolates showed biofilm production. Percentage of biofilm formation was highest in P. aeruginosa (63.15%). Conclusion: Tube test method was found to be more reliable method. The in vitro antibiotic susceptibility pattern of biofilm producing organisms showed less sensitivity as compared to non-biofilm producing organisms.

Self-renewal capacity of semi-differentiated CD8+ T cells sustains long-term protective responses in chronic persistent infection.

CD8 + T lymphocytes have a major role in the elimination of target cells infected by intracellular pathogens, and transformed cells expressing oncoantigens. This happens when host nucleated cells are able to present proteasome-derived antigens or indirectly cross-presented peptide antigens in association with major histocompatibility complex (MHC) class I molecules (1). Upon recognition of the MHC-peptide complexes by CD8 + T cells via their antigen receptors (TCR), cytotoxic lymphocytes release granules containing perforins and granzymes that cause direct damage to target cells, as well as expressed factors such as the Fas ligand and tumor necrosis factor-alpha (TNF-α) that induce apoptosis, thus preventing the spread of infection or tumor growth (2). It is noteworthy that the function of CD8 + T lymphocytes is not limited to eliminating target cells, these cells also participate in other mechanisms of host defense, mainly through the production of interferon-gamma (IFN-γ). IFN-γ has the ability to directly inhibit viral replication, activate macrophages by increasing its cytotoxic and antigen presenting capacity, and may further induce the synthesis of class I MHC molecules as well as other proteins involved in antigen processing and presentation (2).