Interleukin-37 (IL-37), a member of the IL-1 family, primarily functions as an anti-inflammatory cytokine, reducing inflammation and suppressing the immune response. However, the expression and role of IL-37 in tuberculosis (TB) remains unknown. We aimed to measure serum levels of IL-37 and several important cytokines in 25 patients with active TB and to analyse their association with disease activity. We found that IL-37 levels decreased in patients with TB and recovered after treatment. IL-37 levels negatively correlated with the serum concentration of IFN-c and IL-12 but positively correlated with IL-10 and TGFb levels. After IL-37, secretion was blocked in peripheral blood mononuclear cells from active patients with TB, IFN-c and IL-10 production was significantly upregulated; this was not observed in healthy donors or patients after treatment. IL-37 knockdown significantly enhanced the phagocytic activity of THP1-derived macrophages towards Mycobacterium tuberculosis (M. tb). M1/M2 polarization-associated markers were detected simultaneously, and IL-37 induced a phenotypic shift in THP1-derived macrophages towards a high CD206 + and low CD86 + macrophage subtype. Furthermore, this phenotypic shift was accompanied by upregulated mRNA levels of arginase 1, TGF-b and IL-10, which are characteristic hallmarks of M2 macrophages. In conclusion, our results suggest that increased levels of IL-37 in patients with TB are associated with IFN-c, IL-12, IL-10 and TGF-b levels and that IL-37 plays a pathological role in TB infection by inhibiting the production of pro-inflammatory cytokines and inducing macrophages towards an M2-like phenotype. Thus, IL-37 may be a novel research target to understand the pathogenesis of TB infection.

Background: Adaptive immune responses that mediate protection against Chlamydia trachomatis (CT) remain poorly defined in humans. Animal chlamydia models have demonstrated that CD4+ Th1 cytokine responses mediate protective immunity against reinfection. To better understand protective immunity to CT in humans, we investigated whether select CT-specific CD4+ Th1 and CD8+ T cell cytokine responses were associated with protection against CT reinfection in women.Methods: Peripheral blood mononuclear cells were collected from 135 CT-infected women at treatment and follow-up visits and stimulated with CT antigens. CD4+ and CD8+ T-cells expressing IFN-γ, TNF-α, and/or IL-2 were assessed using intracellular cytokine staining and cytokine responses were compared between visits and between women with vs. without CT reinfection at follow-up.Results: A CD4+TNF-α response was detected in the majority (77%) of study participants at the treatment visit, but a lower proportion had this response at follow-up (62%). CD4+ IFN-γ and CD4+ IL-2 responses occurred less frequently at the treatment visit (32 and 18%, respectively), but increased at follow-up (51 and 41%, respectively). CD8+ IFN-γ and CD8+ TNF-α responses were detected more often at follow-up (59% for both responses) compared to the treatment visit (30% for both responses). At follow-up, a CD4+IFN-γ response was detected more often in women without vs. with reinfection (60 vs. 33%, P = 0.005).Conclusions: Our findings suggest that a CT-specific CD4+ IFN-γ response is associated with protective immunity against CT reinfection and is thus an important component of adaptive immunity to CT in women.

ObjectiveThe highly conserved 14‐3‐3 proteins interact with key players involved in Parkinson's disease (PD) and other neurodegenerative disorders. We recently demonstrated that 14‐3‐3 phosphorylation is increased in PD models and that increased 14‐3‐3 phosphorylation reduces the neuroprotective effects of 14‐3‐3 proteins. Here, we investigated whether 14‐3‐3 phosphorylation is altered in postmortem brains from control, PD, Alzheimer's Disease (AD), Alzheimer's with Lewy Bodies (ADLB), Dementia with Lewy Bodies (DLB), and Progressive Supranuclear Palsy (PSP) subjects at three conserved sites: serine 58 (S58), serine 185 (S185), and serine 232 (S232).MethodsS58, S185, and S232 phosphorylation was measured by western blot analysis of Triton X‐100 soluble and insoluble fractions from postmortem temporal cortex.ResultsThe ratio of soluble phospho‐S232 to insoluble phospho‐S232 was reduced by 32%, 60%, 37%, and 52% in PD, AD, ADLB, and DLB, respectively. S185 and S58 phosphorylation were mildly elevated in the soluble fraction in DLB. We also noted a dramatic reduction in soluble pan 14‐3‐3 levels by ~35% in AD, ADLB, and DLB. Lower ratios of soluble to insoluble S232 phosphorylation (pointing to higher insoluble pS232) correlated with lower soluble pan 14‐3‐3 levels, suggesting that S232 phosphorylation may promote insolubilization of 14‐3‐3s. The phospho‐S232 ratio and soluble pan 14‐3‐3 levels correlated with clinical and pathological severity.InterpretationThese data reveal dysregulation of 14‐3‐3 proteins in neurodegeneration associated with Lewy body or Alzheimer pathology. S232 phosphorylation may drive insolubilization of 14‐3‐3s and thus contribute to the pathophysiology in neurodegenerative disorders associated with Lewy body or Alzheimer pathology.

The aims of this study were to: 1) determine prevalence of anogenital and oral HPV, 2) determine concordance between HPV at anal, perianal, scrotal/penile, and oral sites; and 3) describe factors associated with anogenital HPV types targeted by the 9-valent vaccine. Data were collected from 2012 to 2015 among men who have sex with men 18–26 years of age enrolled in a vaccine trial (N = 145). Penile/scrotal, perianal, anal, and oral samples were tested for 61 HPV types. Logistic regression was used to identify factors associated with types in the 9-valent vaccine. Participants’ mean age was 23.0 years, 55.2% were African-American, and 26.2% were Hispanic; 93% had anal, 40% penile, and 6% oral HPV. Among those with anogenital infection, 18% had HPV16. Concordance was low between anogenital and oral sites. Factors independently associated with a 9-valent vaccine-type HPV were: race (African-American vs. White, OR=2.67, 95% CI=1.11–6.42), current smoking (yes vs. no, OR=2.37, 95% CI=1.03–5.48), and number of recent receptive anal sex partners (2+ vs. 0, OR=3.47, 95% CI=1.16–10.4). Most MSM were not infected with HPV16 or HPV18, suggesting that they may still benefit from HPV vaccination, but anogenital HPV was very common, highlighting the importance of vaccinating men before sexual initiation.Clinical trial numberNCT01209325

No abstract