Functional IRGM polymorphism is associated with language impairment in glioma and upregulates cytokine expressions.

Immunity-related GTPase family M protein (IRGM) is a human protein recently highlighted for its contribution to autophagy upon infections. Evidences have shown that IRGM may also play critical roles in the pathogenesis of cancer. However, correlation between IRGM and glioma remains unclear. In the current study, we investigated two IRGM genetic polymorphisms, rs10065172C/T and rs13361189T/C, in glioma and their effects on cytokine expression. Data showed that prevalences of rs13361189TC genotype were significantly increased in glioma patients than in healthy controls (odds ratio (OR) = 1.53, 95 % confidence interval (CI) 1.05-2.24, P = 0.028), and frequency of polymorphic rs13361189CC genotype was further elevated (OR = 2.43, 95 % CI 1.43-4.14, P = 0.001). Interestingly, rs13361189TC and CC genotypes revealed a strong association with language impairment in glioma patients (OR = 2.16, P = 0.023; OR = 3.71, P = 0.001, respectively). When analyzing these two polymorphisms with related cytokine expression, we observed that subjects carrying rs13361189CC genotype had higher serum level of interferon-gamma (IFN-γ) than those with wild-type TT genotype (P < 0.01). In addition, subjects with rs13361189TC and CC genotypes presented elevated serum level of interleukin 4 (IL-4) than those with TT genotype. These data indicate a potential role of IRGM in the development of glioma probably by affecting IFN-γ and IL-4.

IL-10-producing B cells are induced early in HIV-1 infection and suppress HIV-1-specific T cell responses.

A rare subset of IL-10-producing B cells, named regulatory B cells (Bregs), suppresses adaptive immune responses and inflammation in mice. In this study, we examined the role of IL-10-producing B cells in HIV-1 infection. Compared to uninfected controls, IL-10-producing B cell frequencies were elevated in both blood and sigmoid colon during the early and chronic phase of untreated HIV-1 infection. Ex vivo IL-10-producing B cell frequency in early HIV-1 infection directly correlated with viral load. IL-10-producing B cells from HIV-1 infected individuals were enriched in CD19(+)TIM-1(+) B cells and were enriched for specificity to trimeric HIV-1 envelope protein. Anti-retroviral therapy was associated with reduced IL-10-producing B cell frequencies. Treatment of B cells from healthy donors with microbial metabolites and Toll-like receptor (TLR) agonists could induce an IL-10 producing phenotype, suggesting that the elevated bacterial translocation characteristic of HIV-1 infection may promote IL-10-producing B cell development. Similar to regulatory B cells found in mice, IL-10-producing B cells from HIV-1-infected individuals suppressed HIV-1-specific T cell responses in vitro, and this suppression is IL-10-dependent. Also, ex vivo IL-10-producing B cell frequency inversely correlated with contemporaneous ex vivo HIV-1-specific T cell responses. Our findings show that IL-10-producing B cells are induced early in HIV-1 infection, can be HIV-1 specific, and are able to inhibit effective anti-HIV-1 T cell responses. HIV-1 may dysregulate B cells toward Bregs as an immune evasion strategy.