Th1 Immune Response Research Articles

L-Theanine prevents ulcerative colitis by regulating the CD4+ T cell immune response through the gut microbiota and its metabolites.

The disturbance of gut microbiota and its metabolites are considered to be the causes of ulcerative colitis (UC), which leads to immune abnormalities. Diet is the most important regulator of gut microbiota; therefore, it has a beneficial impact on UC. A novel food ingredient, L-theanine, alters the gut microbiota, thereby regulating gut immunity. However, whether L-theanine prevents UC by altering the gut microbiota, as well as the underlying mechanisms, remains unknown. Here, L-theanine was used to optimize the gut microbiota and its metabolites. Furthermore, to explore the mechanism by which L-theanine prevents UC, an L-theanine fecal microbiota solution was used to prevent dextran sulfate sodium-induced UC via fecal microbiota transplantation. Improvements in the colonic structure, colon histology scores, immune factors (IL-10), and inflammatory factors (IL-1β) demonstrated the preventive effect of L-theanine on UC. The 16S rDNA and metabolomic results showed that tryptophan-, short chain fatty acid-, and bile acid-related microbiota, such as Muribaculaceae, Lachnospiraceae, Alloprevotella, and Prevotellaceae were the dominant. Flow cytometry results showed that L-theanine decreased helper T (Th)1 and Th17 immune responses, and increased Th2 and T-regulatory immune responses via regulation of antigen-presenting cell responses, such as dendritic cells and macrophages. Therefore, L-theanine regulated the immune response of colon CD4 + T cells to dendritic cell and macrophage antigen presentation via tryptophan-, short chain fatty acid-, and bile acid-related microbiota, thereby preventing dextran sulfate sodium-induced UC.

An Assessment of BHLHE40 Transcription Factor Level and its Target Cytokines in Patients with Rheumatoid Arthritis.

Basic helix-loop-helix protein 40 (BHLHE40) can function as both a transcriptional activator and repressor. Recent studies have reported its regulatory functions in T helper (Th)1 and Th17 immune responses. Rheumatoid arthritis (RA) is an autoimmune inflammatory disease in which joints are involved. Both Th1 and Th17 contribute to the pathogenesis of the disease. In the present study, the levels of BHLHE40, interleukin 17 (IL-17), and interferon-gamma (IFN-γ) were assessed in the RA patients. Two groups, including RA patients and healthy individuals, were included in the study. The relative expression levels of BHLHE40, IL-17, and IFN-γ were quantified in peripheral blood mononuclear cells (PBMCs) using real-time PCR. The results showed that the level of BHLHE40 was significantly higher in RA patients compared to the healthy control (P < 0.001) (11.1-fold increase). Accordingly, a significant increase in the levels of IL-17 (8.1 folds increase) (P < 0.021) and IFN-γ (12.7 folds) (P < 0.001) was observed. Evaluation of the expression level of BHLHE40 in RA patients showed a significant increase. In line with the elevated level of BHLHE40, a significant increase in the expression level of IL-17 and IFN-γ was also detected. These findings point to the possible role of BHLHE40 in the disease course or severity by elevating the levels of inflammatory cytokines, including IL-17 and IFN-γ. Therefore, BHLHE40 might be considered either as a putative biomarker or as a candidate for therapy in a variety of human diseases.

Canthaxanthin ameliorates atopic dermatitis in mice by suppressing Th2 immune response.

Atopic dermatitis (AD) is a prevalent chronic inflammatory skin disorder characterized by intense pruritus and complex immunopathogenic mechanisms. Recent evidence has highlighted the critical link between dysregulated intestinal microecology and altered immune responses in AD progression. As essential components of the intestinal microenvironment, metabolites play pivotal roles in various physiological processes. Through metabolomic profiling in an AD mouse model, we identified a significant reduction in canthaxanthin (CTX), a bacterial-derived metabolite naturally present in many foods, in AD mice compared to healthy controls. To investigate the therapeutic potential of CTX, we established an AD model by repeatedly applying 2,4-dinitrochlorobenzene (DNCB) to the ears and dorsal skin of mice, successfully inducing AD-like symptoms and lesions. Notably, oral administration of CTX significantly attenuated skin inflammation and reduced serum IgE levels in this DNCB-induced AD model. Both in vivo and in vitro studies demonstrated that CTX treatment effectively suppressed Th2 immune responses. Mechanistically, we found that CTX significantly inhibited the activation of the JAK2-STAT6 signaling pathway in Th2-polarized T cells. Our findings not only demonstrate the therapeutic efficacy of CTX in AD but also elucidate its molecular mechanism in modulating T helper cell subset balance. These insights suggest that CTX could serve as a promising therapeutic agent for AD and potentially other Th2 response-mediated immune disorders.

Genetic background and microbiome drive susceptibility to epicutaneous sensitization and food allergy in adjuvant-free mouse model

BackgroundThe dual allergen exposure hypothesis states that sensitization to food antigens occurs through a damaged skin barrier in individuals with no previous oral tolerance to certain foods. However, the resulting allergic reaction could depend on factors such as the host’s genetic predisposition as well as the skin and gut microbiota.MethodsSpecific-pathogen-free BALB/c and C57BL/6 and germ-free (GF) BALB/c mice were epicutaneously sensitized with ovalbumin (OVA) via dorsal tape-stripped skin and challenged with OVA by intragastric gavage. The development of food allergy (FA) symptoms, the Th2 and mast cell immune response and differences in the skin and gut microbiota were investigated.ResultsBALB/c mice, but not C57BL/6 mice, showed severe clinical signs of FA (hypothermia, diarrhea) as well as a stronger serum antibody response and Th2 cytokine secretion in the spleen and jejunum after OVA-treatment. The increased mast cell count correlated with higher MCPT-1 production and histidine decarboxylase mRNA expression in the jejunum of these mice. The 16S rRNA sequencing analysis revealed lower abundance of short-chain fatty acids producing bacteria in the gut microbiome of OVA-treated BALB/c mice. Changes in the β-diversity of the gut microbiome reflect both the genetic background as well as the OVA treatment of experimental mice. Compared to SPF mice, GF mice developed more severe anaphylactic hypothermia but no diarrhea, although they had a higher mast cell count, increased MCPT-1 production in the jejunum and serum, and increased arachidonate 5-lipoxygenase mRNA expression.ConclusionsWe show that the BALB/c mice are a mouse strain of choice for model of adjuvant-free epicutaneous sensitization through the disrupted skin barrier and following food allergy development. Our results highlight the significant influence of genetic background and microbiota on food allergy susceptibility, emphasizing the complex interplay between these factors in the allergic response.

Reductive Adjuvant Nanosystem for Alleviated Atopic Dermatitis Syndromes.

Atopic dermatitis (AD) is a recurrent and chronic inflammatory skin condition characterized by a high lifetime prevalence and significant impairment of patients' quality of life, primarily due to intense itching and discomfort. However, current pharmacological interventions provide only moderate efficacy and are frequently accompanied by adverse side effects. The immune-pathogenesis of AD involves dysregulation of the Th2 immune response and exacerbation of inflammation related to excessive reactive oxygen species (ROS). Therefore, to address these issues, in this study, we targeted the upstream pathogenesis by designing a pro-Th1 adjuvant nanoemulsion loaded with poly(I:C) and encapsulated with the ROS-scavenger vitamin E, termed PV-NE. PV-NE effectively rebalanced the Th1/Th2 immune response and reduced ROS levels both in vivo and ex vivo, leading to the restoration of immune balance in AD-affected skin and alleviation of symptoms such as lichenification and erythematous patches. In conclusion, our development of the reductive adjuvant nanosystem PV-NE demonstrates its biocompatibility and efficacy in combating AD progression without the use of immunosuppressant glucocorticoids. This has the potential to significantly impact the design and enhancement of pharmacotherapy in future clinical research aimed at curing AD.

Molecular and Immunological Characterization of Troponin C: An Allergen from Scylla paramamosain.

Scylla paramamosain, a crustacean of substantial importance, is a frequent trigger of food allergies. This study examined the molecular and immunological properties of troponin C from S. paramamosain (Scy p TnC) as an allergen. The findings indicated that thermal stability of Scy p TnC comprised 150 amino acids and facilitated the induction of CD63/CD203c in basophils from crab allergy patients. Furthermore, treatment of Scy p TnC with chemical denaturants caused structural degradation, which resulted in diminished IgG binding capacity. Subsequently, 6 linear epitopes and 4 conformational epitope regions of TnC were predicted, with epitopes at the C-terminal being conserved throughout 9 discovered TnCs. Concurrently, mice sensitized with Scy p TnC exhibited markedly increased levels of IgE and IL-4 release, provoking a Th2 immune response. The results reveal crab allergens and enhance existing knowledge regarding allergenic components in crabs, thereby facilitating the advancement of molecular diagnostics and targeted therapeutic strategies.

Fitness costs of Mycobacterium tuberculosis resistant to rifampicin is compensated by rapid Th2 polarization mediated by early and high IL-4 production during mice infection

It was a general belief that drug resistance in Mycobacterium tuberculosis (Mtb) was associated with lesser virulence, particularly rifampicin resistance, which is usually produced by mutations in the RNA polymerase Beta subunit (RpoB). Interestingly, this kind of bacterial mutations affect gene transcription with significant effects on bacterial physiology and metabolism, affecting also the bacterial antigenic constitution that in consequence can produce diverse immune responses and disease outcome. In the present study, we show the results of the Mtb clinical isolate A96, which is resistant to rifampicin and when used to infect BALB/c mice showed hypervirulence, apparently by rapidly polarization of the Th2 immune response through early and high production of IL-4. The 2D-PAGE analysis of the secretome of Mtb A96 showed 204 spots, and by immunoproteome, seven proteins that were differentially recognized with the sera of infected mice on day 28 were identified by LC-MS/MS. The proteins correspond to surface antigens, virulence factors, and energy metabolism enzymes. Some of them are immunodominant antigens, such as LpqH lipoprotein that induces IL-4 secretion in cell suspensions from the lung and spleen of mice infected with Mtb A96 at 28 days postinfection, suggesting that LpqH could be one of the main antigens involved in the Th2 polarization. The reduction of Mtb A96 hypervirulence in IL-4Rα−/− BALB/c mice highlights the importance of IL-4 induction and Th2 response polarization and the immunopathological response. Thus, high and rapid bias to Th2 response is a mechanism of Mtb virulence, which could be mediated by rifampicin-resistant Mtb isolates, probably by high production and secretion of specific antigens.

STAT6 deficiency mitigates the severity of pulmonary arterial hypertension caused by chronic intermittent hypoxia by suppressing Th2-inducing cytokines

BackgroundObstructive sleep apnea (OSA) is frequently associated with increased incidence and mortality of pulmonary hypertension (PH). The immune response contributes to pulmonary artery remodeling and OSA-related diseases. The immunologic factors linked to OSA-induced PH are not well understood. STAT6 is crucial in the signaling pathway that modulates immune response. However, the status of phosphorylated STAT6 (p-STAT6) in an OSA-induced PH mouse model remains largely unexplored.MethodsChronic intermittent hypoxia (CIH) plays a crucial role in the progression of OSA. This study utilized a in vivo CIH model to examine the role of STAT6 in CIH-induced PH.ResultsCIH mice exhibited pulmonary artery remodeling and pulmonary hypertension, indicated by increased right ventricular systolic pressure (RVSP), higher right ventricular to left ventricular plus septum (RV/LV + S) ratios, and significant morphological alterations compared to normoxic (Nor) mice. Increased p-STAT6 in the lungs and elevated p-STAT6 + IL-4 + producing T cells in CIH mice. STAT6 deficiency (STAT6-/-) improved PH and PA remodeling in CIH-induced PH mouse models.STAT6 deficiency impaired the T helper 2 (Th2) immune response, affecting IL-4 and IL-13 secretion. IL-4, rather than IL-13, activated STAT6 in human pulmonary artery smooth muscle cells (hPASMCs). STAT6 knockdown decreased the proliferation in IL-4 treated hPASMCs.ConclusionThese findings exhibit the critical role of STAT6 in the pathogenesis of CIH induced PH by regulating Th2 immune response.STAT6 could be a significant therapeutic target for OSA-related PH.

Regulation of fibronectin and collagens type I, III and VI by TNF-α, TGF-β, IL-13, and tofacitinib

Understanding how inflammatory cytokines influence profibrogenic wound healing responses in fibroblasts is important for understanding the pathogenesis of fibrosis. TNF-α and IL-13 are key cytokines in Th1 and Th2 immune responses, respectively, while TGF-β1 is the principal pro-fibrotic mediator. We show that 12-day fibroblast culture with TNF-α or IL-13 induces fibrogenesis, marked by progressively increasing type III and VI collagen formation, and that TGF-β1 co-stimulation amplifies these effects. Tofacitinib substantially reduced the formation of ECM proteins in response to IL-13, while fibrogenesis in response to TNF-α or TGF-β1 was marginally inhibited. The in vitro findings were supported by clinical observations in patients with active rheumatoid arthritis, which had elevated serum type III collagen formation, indicating ongoing fibrogenesis during inflammation. After 48–60 weeks of tofacitinib treatment, type III collagen degradation, aswell as formation, were significantly decreased compared to baseline, highlighting dual anti-inflammatory and anti-fibrogenic effects of tofacitinib. In contrast, other anti-inflammatory treatments including methotrexate, adalimumab and tocilizumab demonstrated anti-inflammatory effects only. Our results highlight fibro-inflammatory profiles associated with TNF-α or IL-13 stimulation, both alone and in combination with TGF-β1, and support the use of tofacitinib as an anti-fibrogenic treatment in chronic inflammatory conditions.

Exploring microRNA-Mediated Immune Responses to Soil-Transmitted Helminth and Herpes Simplex Virus Type 2 Co-Infections.

Over the last two decades, the field of microRNA (miRNA) research has grown significantly. MiRNAs are a class of short, single-stranded, non-coding RNAs that regulate gene expression post-transcriptionally. Thereby, miRNAs regulate various essential biological processes including immunity. Dysregulated miRNAs are associated with various infectious and non-infectious diseases. Recently co-infection with soil-transmitted helminths (STHs) and herpes simplex virus type 2 (HSV-2) has become a focus of study. Both pathogens can profoundly influence host immunity, particularly in under-resourced and co-endemic regions. It is well known that STHs induce immunomodulatory responses that have bystander effects on unrelated conditions. Typically, STHs induce T-helper 2 (Th2) and immunomodulatory responses, which may dampen the proinflammatory T-helper 1 (Th1) immune responses triggered by HSV-2. However, the extent to which STH co-infection influences the host immune response to HSV-2 is not well understood. Moreover, little is known about how miRNAs shape the immune response to STH/HSV-2 co-infection. In this article, we explore the potential influence that STH co-infection may have on host immunity to HSV-2. Because STH and HSV-2 infections are widespread and disproportionately affect vulnerable and impoverished countries, it is important to consider how STHs may impact HSV-2 immunity. Specifically, we explore how miRNAs contribute to both helminth and HSV-2 infections and discuss how miRNAs may mediate STH/HSV-2 co-infections. Insight into miRNA-mediated immune responses may further improve our understanding of the potential impact of STH/HSV-2 co-infections.

ЦИТОКИНОВЫЙ ПРОФИЛЬ МЫШЕЙ C57BL/6 С МОДЕЛИРОВАННОЙ ОПУХОЛЬЮ МЕЛАНОМЫ ПРИ ВВЕДЕНИИ ЭКСТРАКТА PHLOJODICARPUS SIBIRICUS

The article investigates the effect of Phlojodicarpus sibiricus extract on the cytokine status of C57Bl/6 mice with transplanted melanoma. Phlojodicarpus sibiricus, also known as the Siberian phlojodicarpus, is a perennial herbaceous plant belonging to the Apiaceae family. It is widely distributed in Siberia and the Russian Far East. The extract was administered orally at a dosage of 100 mg/ml, and the concentrations of cytokines such as IL-2, IL-4, IL-5, IL-10, IL-12, TNF-α, IFN-γ, and GM-CSF were assessed. The experiment included three groups of mice: a control group, a tumor group, and a tumor plus extract group. The results of our experimental investigation indicate the complexity of changes in the cytokine profile of mice with modeled melanoma. Mice with tumors showed elevated levels of IL-4 and reduced levels of IL-5 compared to the control group, suggesting a predominance of the Th1/Th2 balance towards a Th2 immune response. Additionally, the high concentration of IFN-γ indicates active participation of the Th1 response, highlighting the intricate dynamics of cytokine interactions in the context of tumor growth. Analysis of the cytokine profile in mice receiving the extract orally showed that the level of IFN-γ was statistically significantly lower than that in the tumor group and remained similar to that of the control group. The mechanism underlying the suppression of this cytokine production may be related to the low level of IL-12. Overall, the cytokine levels in mice treated with the extract showed signs of a predominance of the Th2 immune response. These results open new prospects for the targeted use of the extract in melanoma immunotherapy and warrant further investigation into its mechanisms of action on various components of the immune system.

Transcriptomic differences between the spleens of mice immunized with inactivated antigens of foot-and-mouth disease virus and Senecavirus A

The aim of this study was to compare the immune responses of C57BL/6 mice immunized with two pathogens, foot-and-mouth disease virus (FMDV) and Senecavirus A (SVA), and to provide clues for revealing the regulatory mechanisms of acquired immunity. Inactivated and purified FMDV and SVA antigens were used to immunize C57BL/6 mice respectively, and the mice immunized with PBS were taken as the control. The percentages of Th1 and Th2 cells in the spleen lymphocytes of mice in each group were analyzed by flow cytometry at 14 and 28 days after immunization. RNA-Seq was performed for the spleen. Mouse macrophages were stimulated with the antigens in vitro to examine the expression of the differentially expressed genes (DEGs) screened out. The results showed that 14 days after immunization, there was no significant difference in the magnitude of the Th1/Th2 immune response elicited by the FMDV and SVA antigens. After 28 days, the magnitudes of the Th1 and Th2 immune responses elicited by the SVA antigen were higher than those elicited by the FMDV antigen. RNA-Seq revealed two common DEGs, Rsad2 and Tspan8, between the two immunization groups, which indicated that the two genes may be involved in the activation of the Th1/Th2 immune responses by FMDV and SVA antigens. FMDV and SVA antigens stimulated macrophages to secrete interleukin (IL)-12 and IL-33 in vitro, and the expression of Tspan8 and Rsad2 was consistent with the RNA-Seq results. The expression of Rsad2 was regulated by type I interferons (IFNα, IFNβ). In this study, we obtained the DEGs involved in the immune responses to the two antigens in mouse spleen, which provides a molecular basis for investigating the immune response mechanisms induced by FMDV and SVA.

Role of the Anaphase-Promoting Complex Activator Cdh1 in the Virulence of Cryptococcus neoformans.

Cryptococcus neoformans is a globally distributed human fungal pathogen that can cause cryptococcal meningitis with high morbidity and mortality. In this study, we identified an anaphase-promoting complex (APC) activator, Cdh1, and examined its impact on the virulence of C. neoformans. Our subcellular localization analysis revealed that Cdh1 is situated in the nucleus of C. neoformans. Disrupting or overexpressing the CDH1 gene caused abnormal capsule formation in C. neoformans. The cdh1Δ mutant displayed slight sensitivity when grown at 37 °C, indicating that Cdh1 plays a role in maintaining the growth of C. neoformans at 37 °C. A fungal virulence assay showed that Cdh1 is closely associated with the virulence of C. neoformans, and both the cdh1Δ mutant and CDH1OE overexpression strains significantly diminished the virulence of C. neoformans. The Cryptococcus-macrophage interaction assay revealed that both the cdh1∆ mutant and the CDH1OE strains had significantly lower proliferation ability inside macrophages. Furthermore, the infection of the cdh1Δ mutant significantly activated neutrophil recruitment, as well as Th2 and Th17 immune responses, in lung tissue. In summary, our findings indicate that Cdh1 is crucial for producing virulence factors and fungal virulence in C. neoformans. The findings of this study can offer valuable insights and form the basis for further study of the regulatory mechanisms governing the pathogenicity of C. neoformans, potentially leading to the development of novel therapeutic strategies.

Cannabichromene as a Novel Inhibitor of Th2 Cytokine and JAK/STAT Pathway Activation in Atopic Dermatitis Models.

Cannabichromene (CBC) is one of the main cannabinoids found in the cannabis plant, and although less well known than tetrahydrocannabinol (THC) and cannabidiol (CBD), it is gaining attention for its potential therapeutic benefits. To date, CBC's known mechanisms of action include anti-inflammatory, analgesic, antidepressant, antimicrobial, neuroprotective, and anti-acne effects through TRP channel activation and the inhibition of inflammatory pathways, suggesting that it may have therapeutic potential in the treatment of inflammatory skin diseases, such as atopic dermatitis (AD), but its exact mechanism of action remains unclear. Therefore, in this study, we investigated the effects of CBC on Th2 cytokines along with the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathways involved in AD pathogenesis. We used a 2,4-Dinitrochlorobenzene (DNCB)-induced BALB/c mouse model to topically administer CBC (0.1 mg/kg or 1 mg/kg). The results showed that skin lesion severity, ear thickness, epithelial thickness of dorsal and ear skin, and mast cell infiltration were significantly reduced in the 0.1 mg/kg CBC-treated group compared with the DNCB-treated group (p < 0.001). In addition, real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis showed a significant decrease in the mRNA expression of Th2 cytokines (TSLP, IL-4, IL-13) and inflammatory mediators (IFN-γ, IL-1β, IL-6, IL-17, IL-18, and IL-33) (p < 0.05). Western blot analysis also revealed a significant decrease in JAK1, JAK2, STAT1, STAT2, STAT3, and STAT6 protein expression (p < 0.05). These results suggest that CBC is a promising candidate for the treatment of AD and demonstrates the potential to alleviate AD symptoms by suppressing the Th2 immune response.

Construction and immunological evaluation of recombinant adenovirus vaccines of new novel NADC34-PRRSV strains in pigs.

Porcine reproductive and respiratory syndrome virus (PRRSV) causes reproductive and respiratory diseases in sow herds and piglets. The emergence of ORF5 RFLP 1-7-4-like (NADC34-like) PRRSV strain in China has brought a new round of challenges to PRRSV prevention. In addition, recombinant adenovirus vaccine candidates against the newly emerged NADC34-like strain were constructed in the study; the immunogenicity of the vaccine was investigated in piglets. After inoculation with PRRSV recombinant adenovirus, specific antibodies, neutralizing antibodies, and levels of IFN-γ and IL-4 cytokines were detected in serum. Thirty-five days after immunization, the levels of IFN-γ and IL-4 cytokines in the pac-Ad5-34-GP3, pac-Ad5-34-GP5, and pac-Ad5-34-GP35 experimental groups were significantly higher (p < 0.05) than those of the PBS and the adenovirus group. All vaccines can cause corresponding Th1 and Th2 immune responses based on animal experimental results. After the challenge, no obvious clinical symptoms were observed in the immune groups compared with the control group, vaccinated animals could reduce the occurrence of viremia, and the occurrence of viremia was alleviated, with no obvious pathological changes in the lungs, indicating that recombinant adenovirus vaccine could provide a good protective immunity and produce a good humoral and cellular immune response at the same time. It shows that the recombinant adenovirus vaccine group has better protection against the virus. Provide vaccine reserve and theoretical support for the emergence of new PRRSV subtypes in China.

Localized provoked vulvodynia as an immune-mediated inflammatory disease: rationale for a new line of research.

Localized provoked vulvodynia (LPV), also called vulvar vestibulitis or provoked vestibulodynia, is a major cause of dyspareunia that severely impacts sexual health. At the tissue level, lymphocytic inflammation and hyperinnervation are characteristic pathological features, explaining the main symptoms and signs. A recent experimental animal study suggests that the histopathological findings of LPV may be due to mucosal CD4 Th17 immune responses to microbial antigens. We hypothesize that LPV is an immune-mediated inflammatory disease and challenge the concept of LPV as a chronic pain syndrome of unknown cause. Since most treatment modalities currently used in LPV are no better than placebo, we therefore warrant future research investigating the possible presence of CD4 Th17 cells and IL17 cytokine in affected tissues together with treatment trials that include inhibitors of the IL17 pathway.

Potential Interactions Between Soil-Transmitted Helminths and Herpes Simplex Virus Type II: Implications for Sexual and Reproductive Health in Sub-Saharan African.

Sub-Saharan Africa (SSA) bears a disproportionate and overlapping burden of soil-transmitted helminths (STHs) and sexually transmitted viral infections. An estimated 232 million pre-school and school-aged children in SSA are vulnerable to STH infections. Together with this, SSA has a high prevalence of herpes simplex virus type II (HSV-2), the primary cause of genital herpes. Studies have examined the immunological interactions between STHs and human immunodeficiency virus and human papillomavirus during co-infections. However, epidemiological and immunological studies on STH-HSV-2 co-infections are lacking, therefore their impact on sexual and reproductive health is not fully understood. STH-driven Th2 immune responses are known to downregulate Th1/Th17 immune responses. Therefore, during STH-HSV-2 co-infections, STH-driven immune responses may alter host immunity to HSV-2 and HSV-2 pathology. Herein, we provide an overview of the burden of STH and HSV-2 infections in SSA, and host immune responses to STH and HSV-2 infections. Further, we emphasize the relevance and urgent need for (i) focused research into the interactions between these important pathogens, and (ii) integrated approaches to improve the clinical detection and management of STH-HSV-2 co-infections in SSA.

Surfactant Protein-A and its immunomodulatory roles in infant respiratory syncytial virus infection: a potential for therapeutic intervention?

The vast majority of early-life hospital admissions globally highlight respiratory syncytial virus (RSV), the leading cause of neonatal lower respiratory tract infections, as the major culprit behind the poor neonatal outcomes following respiratory infections. Unlike those of older children and adults, the immune system of neonates looks rather unique, therefore mostly counting on the innate immune system and antibodies of maternal origins. The collaborations between cells and immune compartments during infancy inclines bias toward a T-helper 2 (Th2) immune profile and thereby away from a T-helper 1 (Th1) immune response. What makes it more problematic is that RSV infection also tends to elicit a stronger Th2-biased immune response and drive an aberrant allergy-like inflammation. It is thus evident how RSV infections potentially pave the way for wheezing recurrences and childhood asthma later in life. Surfactant, the essential lung substance for normal breathing processes in mammals, has immunomodulatory properties including lung collectins such as Surfactant Protein-A (SP-A), which is the most abundant protein component of surfactant, and also Surfactant Protein-D (SP-D). Deficiency of SP-A and SP-D has been found to be associated with impaired pathogen clearance and exacerbated immune responses during infections. We therefore conducted a review of the literature to describe pathomechanisms of RSV infections during blunted neonatal immunity potentially facilitating allergy-like inflammatory events within the developing lungs and highlight the potential protective role of the humoral collectin SP-A to mitigate these in the "early in life" pulmonary immune system.

Soy Protein and Safflower-Seed Oil Attenuate Inflammation and Immune Dysfunction in Rats with Hyperuricemia.

A plant-based diet is considered a promising approach for managing hyperuricemia (HUA). This study examined the effects of soy protein and plant-based oils on HUA-induced inflammation and immune dysfunction. Male Wistar rats, induced with HUA using oxonic acid and uric acid (UA), were fed casein or soy protein with palm or safflower oil (2 × 2 factorial design) for 8 weeks. HUA rats had lower serum albumin and T cell percentages in peripheral blood leukocytes (PBLs) and splenocytes, along with increased leukocyte counts and spleen weights, compared to healthy rats (p < 0.05). Soy protein improved HUA-induced reductions in albumin, while safflower-seed oil ameliorated reductions in albumin, plasma interleukin (IL)-4, and T-suppressor splenocytes, and mitigated elevated serum UA, plasma IL-6, and B leukocytes (two-way ANOVA, p < 0.05). In PBL, soy protein alleviated HUA-induced decreases in TNF-α, casein and palm oil increased IL-6, and casein further reduced IFN-γ production. Under Con A stimulation, casein and safflower-seed oil alleviated decreases in IL-6 and IL-10, respectively, while under LPS stimulation, casein further increased TNF-α production. In splenocytes, soy protein and safflower-seed oil reduced HUA-induced increases in TNF-α and increased IL-10, and safflower-seed oil increased IL-6 production. Under Con A stimulation, soy protein and safflower-seed oil reduced TNF-α and increased IL-10 production in splenocytes. The findings suggest that soy protein and safflower-seed oil may counteract HUA-related inflammation, alleviate monocyte activation, and enhance Th2 immune response in HUA. A plant-based diet rich in soy protein and safflower-seed oil may help manage HUA and associated inflammation and immune dysfunction.

Identification and expression analysis of Th2 immune-related gene IL4/13A in turbot (Scophthalmus maximus).

Th2 immunity is a primary host defense against extracellular pathogens, and different IL4/13 paralogues are involved in this immune response in fish. Here, we identified IL4/13A for further Th2 immune response providing information in turbot. The results showed that the full length of the IL4/13A gene is 1,333 bp, containing a 432-bp open reading frame (ORF) that encoded 144 amino acids. Phylogenetic analysis recently showed that turbot IL4/13A has a relationship with Dicentrarchus labrax. Moreover, syntenic analysis revealed similar neighboring genes associated with turbot IL4/13A, compared with other teleosts and mammals. In addition, IL4/13A was widely expressed in all examined tissues with the highest expression level in skin, followed by liver and gill. Finally, IL4/13A showed a general trend of upregulation in immune tissues following bacterial challenge. The significant quick induction of IL4/13A indicated its key roles to prevent pathogens. Characterizations of IL4/13A will probably contribute to understanding of Th2 immunity in fish.