Distinct cytokine patterns in Occult Hepatitis C and Chronic Hepatitis C Virus Infection

Background & Aim: 
The immunopathogenesis of chronic hepatitis C virus (HCV) infection is a matter of great controversy. The imbalance of T-helper lymphocyte cell cytokine production was believed to play an important pathogenic role in chronic viral hepatitis. Occult hepatitis C infection is regarded as a new entity that should be considered when diagnosing patients with a liver disease of unknown origin. The aim of this study was to determine serum T-helper 1 and T-helper 2 cytokine production in patients with occult HCV infection and its role in pathogenesis versus chronic viral hepatitis C infection.

Methods: 
Serum levels of cytokines of T-helper 1 (IL-2, IFN-[gamma]) and T-helper 2 (IL-4) were measured in 27 patients with occult HCV infection and 50 patients with chronic hepatitis C infection.

Results: 
The levels of the T-helper 1 cytokines, IL-2 and IFN-[gamma], were highly and significantly increased in patients with chronic HCV infection as compared with occult HCV infection (p<0.001). The T-helper 2 cytokine IL-4 was highly and significantly increased in occult HCV infection as compared with chronic HCV infection (p<0.001). Necroinflammation (P<0.001) fibrosis (P<0.001) and cirrhosis (P =0.03) were significantly increased in chronic HCV than occult HCV. 

Conclusion: 
Patients with occult HCV infection exhibited distinct immunoregulatory cytokine patterns, favoring viral persistence in the liver in spite of its absence from peripheral blood and explaining the less aggressive course of this disease entity than chronic hepatitis C virus infection

Divergent Annexin A1 expression in periphery and gut is associated with systemic immune activation and impaired gut immune response during SIV infection.

HIV-1 disease progression is paradoxically characterized by systemic chronic immune activation and gut mucosal immune dysfunction, which is not fully defined. Annexin A1 (ANXA1), an inflammation modulator, is a potential link between systemic inflammation and gut immune dysfunction during the simian immunodeficiency virus (SIV) infection. Gene expression of ANXA1 and cytokines were assessed in therapy-naïve rhesus macaques during early and chronic stages of SIV infection and compared with SIV-negative controls. ANXA1 expression was suppressed in the gut but systemically increased during early infection. Conversely, ANXA1 expression increased in both compartments during chronic infection. ANXA1 expression in peripheral blood was positively correlated with HLA-DR+CD4+ and CD8+ T-cell frequencies, and negatively associated with the expression of pro-inflammatory cytokines and CCR5. In contrast, the gut mucosa presented an anergic cytokine profile in relation to ANXA1 expression. In vitro stimulations with ANXA1 peptide resulted in decreased inflammatory response in PBMC but increased activation of gut lymphocytes. Our findings suggest that ANXA1 signaling is dysfunctional in SIV infection, and may contribute to chronic inflammation in periphery and with immune dysfunction in the gut mucosa. Thus, ANXA1 signaling may be a novel therapeutic target for the resolution of immune dysfunction in HIV infection

Modulation of the CD8+-T-cell response by CD4+ CD25+ regulatory T cells in patients with Hepatitis B virus infection

CD4+ CD25+ regulatory T cells have been shown to maintain peripheral tolerance against self and foreign antigens. In this study we analyzed the effect of circulating CD4+ CD25+ T cells on CD8+-T-cell responses of patients with chronic and resolved hepatitis B virus (HBV) infection. We demonstrated that circulating CD4+ CD25+ T cells modulate the function and expansion of HBV-specific CD8+ cells ex vivo in all patients, regardless of whether they have chronic or resolved HBV infection. The possible role of CD4+ CD25+ T cells in the pathogenesis of chronic HBV infection is not supported by these data. However, these results might have implications for optimizing future immunotherapeutic approaches to HBV treatment

Differentiation and Protective Capacity of Virus-Specific CD8

Noroviruses can establish chronic infections with active viral shedding in healthy humans but whether persistence is associated with adaptive immune dysfunction is unknown. We used genetically engineered strains of mouse norovirus (MNV) to investigate CD8+ T cell differentiation during chronic infection. We found that chronic infection drove MNV-specific tissue-resident memory (Trm) CD8+ T cells to a differentiation state resembling inflationary effector responses against latent cytomegalovirus with only limited evidence of exhaustion. These MNV-specific Trm cells remained highly functional yet appeared ignorant of ongoing viral replication. Pre-existing MNV-specific Trm cells provided partial protection against chronic infection but largely ceased to detect virus within 72 hours of challenge, demonstrating rapid sequestration of viral replication away from T cells. Our studies revealed a strategy of immune evasion by MNV via the induction of a CD8+ T cell program normally reserved for latent pathogens and persistence in an immune-privileged enteric niche. Chronic infections often cause T cell dysfunction, but how noroviruses (NV) evade immunity is unknown. Tomov et al. show that gut-resident T cells against NV remain functional but ignorant of chronic viral replication, suggesting that NV persists in an immune-privileged enteric niche. © 2017 Elsevier Inc

Chronic Wounds: The Persistent Infection Problem

Chronic wounds heal poorly and can have a huge impact on a sufferer’s life. They are caused by a number of factors, one of which is the presence of persistent infections. Many standard treatments are unsuccessful at destroying these infections as the bacteria form a biofilm. Biofilms encase the bacteria, preventing immune cells from destroying them. There are multiple bacterial species within a biofilm, sometimes with antibiotics resistance, and which species are present changes over time. The changing, multi-species nature of biofilms can make finding an effective antibiotic treatment difficult. Also, bacteria in biofilms genetically differ from planktonic bacteria, and are often less susceptible to antibiotics. Additionally, biofilms are thought to reduce the access of antibiotics to the bacteria within. These reasons are discussed in further detail in this review, along with some of the reasons why bacteria can prevent wound closure

Dynamic MAIT cell response with progressively enhanced innateness during acute HIV-1 infection.

Mucosa-associated invariant T (MAIT) cell loss in chronic HIV-1 infection is a significant insult to antimicrobial immune defenses. Here we investigate the response of MAIT cells during acute HIV-1 infection utilizing the RV217 cohort with paired longitudinal pre- and post-infection samples. MAIT cells are activated and expand in blood and mucosa coincident with peak HIV-1 viremia, in a manner associated with emerging microbial translocation. This is followed by a phase with elevated function as viral replication is controlled to a set-point level, and later by their functional decline at the onset of chronic infection. Interestingly, enhanced innate-like pathways and characteristics develop progressively in MAIT cells during infection, in parallel with TCR repertoire alterations. These findings delineate the dynamic MAIT cell response to acute HIV-1 infection, and show how the MAIT compartment initially responds and expands with enhanced function, followed by progressive reprogramming away from TCR-dependent antibacterial responses towards innate-like functionality

Influence of infection on the distribution patterns of NIH-Chronic Prostatitis Symptom Index scores in patients with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS)

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a complex condition for which the etiological determinants are still poorly defined. To better characterize the diagnostic and therapeutic profile of patients, an algorithm known as UPOINT was created, addressing six major phenotypic domains of CP/CPPS, specifically the urinary (U), psycho-social (P), organ-specific (O), infection (I), neurological/systemic (N) and muscular tenderness (T) domains. An additional sexual dysfunction domain may be included in the UPOINT(S) system. The impact of the infection domain on the severity of CP/CPPS symptoms is a controversial issue, due to the contradictory results of different trials. The aim of the present retrospective study was to further analyze the extent to which a positive infection domain of UPOINTS may modify the pattern of CP/CPPS symptom scores, assessed with the National Institutes of Health-Chronic Prostatitis Symptom Index (NIH-CPSI). In a cohort of 935 patients that was divided on the basis of the presence or absence of prostatic infection, more severe clinical symptoms were shown by the patients with infection (median NIH total score: 24 versus 20 points in uninfected patients; P<0.001). Moreover, NIH-CPSI score distribution curves were shifted towards more severe symptoms in patients with a positive infection domain. Division of the patients into the six most prominent phenotypic clusters of UPOINTS revealed that the 'prostate infection-related sexual dysfunction' cluster, including the highest proportion of patients with evidence of infection (80%), scored the highest number of NIH-CPSI points among all the clusters. To assess the influence of the infection domain on the severity of patients' symptoms, all subjects with evidence of infection were withdrawn from the 'prostate infection-related sexual dysfunction' cluster. This modified cluster showed symptom scores significantly less severe than the original cluster, and the CPSI values became comparable to the scores of the five other clusters, which were virtually devoid of patients with evidence of infection. These results suggest that the presence of pathogens in the prostate gland may significantly affect the clinical presentation of patients affected by CP/CPPS, and that the infection domain may be a determinant of the severity of CP/CPPS symptoms in clusters of patients phenotyped with the UPOINTS system. This evidence may convey considerable therapeutic implications

The Serumal Concentration of Hbsag in Patiets with Chb/hiv Co-infection Comparing with Chb Mono-infection in the Different Phases of Natural Course of Chronic Hepatitis В

The prevalence and inclination to chronization of viral hepatitis B is 3 – 5 times higher in patients with HIV-infection than in HIV-negative ones. The natural clinical course of chronic hepatitis B (CHB) in patients with HIV has the features, connected with immune suppression and mutual influence of viruses. The quantitative determination of HBsAg allows the more precise monitoring of the natural course and the dynamics of treatment of patients with CHB but these features are little studied in patients with co-infection CHB/HIV. In the work was presented the comparative analysis of the results of quantitative determination of the serumal HBsAg in 59 Patients with co-infection CHB/HIV and 60 ones with chronic hepatitis. At the study it was established, that in patients with CHB/HIV co-infection were observed the reliably higher qHBsAg levels than in HIV-negative ones both in whole and in each CHB phase that depends on the immune suppression degree and DNA level of hepatitis B virus

Genetic Variation in the IL-6 and HLA-DQB1 Genes Is Associated with Spontaneous Clearance of Hepatitis C Virus Infection.

Background. Millions of people are infected with hepatitis C virus (HCV) worldwide and 30% spontaneously clear the infection. Reasons for HCV clearance without antiviral treatment are not well understood. Methods. Blood was collected for DNA analysis from patients with chronic HCV infection or evidence of spontaneous clearance. To overcome anticipated limitations of small sample size, primary analyses consisted of a candidate gene analysis of 12 preselected genes based on known association with host immunologic response to HCV infection. To further reduce the impact of multiple testing on power, a single likelihood ratio test was conducted for each gene using all associated SNPs assayed on the Illumina Quad 610/660W chip. Step-down permutation methods were used to adjust for multiple testing in all analyses. Results. Ninety-five and 62 patients with HCV chronic infection or spontaneous clearance, respectively, were included for analysis. HLA-DQB1 (p = 1.76⁎10(-5)) and IL-6 (p = 0.0007) genes were significantly associated with spontaneous HCV clearance. IL-28B was not significantly associated with spontaneous clearance (p = 0.17). Conclusion. Our whole-gene analytic strategy identified a previously unreported association of IL-6 with spontaneous clearance of HCV infection. We also confirmed the finding that HLA-DQB1 is associated with spontaneous resolution of HCV infection

Microbial risk factors of cardiovascular and cerebrovascular diseases: potential therapeutic options

Infection and inflammation may have a crucial role in the pathogenesis of atherosclerosis. This hypothesis is supported by an increasing number of reports on the interaction between chronic infection, inflammation, and atherogenesis. Assessment of serological and inflammatory markers of infection may be useful adjuncts in identifying those patients who are at a higher risk of developing vascular events, and in whom more aggressive treatments might be warranted