Chagas disease is caused by infection with the protozoan Trypanosoma cruzi. CD8 T-lymphocytes help to control infection, but apoptosis of CD8 T cells disrupts immunity and efferocytosis can enhance parasite infection within macrophages. Here, we investigate how apoptosis of activated CD8 T cells affects M1 and M2 macrophage phenotypes. First, we found that CD8 T-lymphocytes and inflammatory monocytes/macrophages infiltrate peritoneum during acute T. cruzi infection. We show that treatment with anti-Fas ligand (FasL) prevents lymphocyte apoptosis, upregulates type-1 responses to parasite antigens, and reduces infection in macrophages cocultured with activated CD8 T cells. Anti-FasL skews mixed M1/M2 macrophage profiles into polarized M1 phenotype, both in vitro and following injection in infected mice. Moreover, inhibition of T-cell apoptosis induces a broad reprogramming of cytokine responses and improves macrophage-mediated immunity to T. cruzi. The results indicate that disposal of apoptotic CD8 T cells increases M2-macrophage differentiation and contributes to parasite persistence.

Background We aimed to evaluate the Neisseria meningitidis C conjugated vaccine (MCC) seroconversion and adverse events (AE) in HIV-infected and uninfected children and adolescents in Rio de Janeiro, Brazil. Methods HIV-infected or uninfected subjects, 2–18 years old, with CD4+ T-lymphocyte cell (CD4) percentage >15%, without active infection or antibiotic use, were enrolled. All patients were evaluated before and 1–2 months after immunization for seroconversion (defined as ≥4-fold titer increase in human serum bactericidal activity), and for AEs at 20 minutes, 3 and 7 days after immunization. Factors associated with seroconversion among HIV-infected group were studied. Results 204 subjects were enrolled: 154 HIV-infected and 50 HIV-uninfected. Median age was 12 years and 53% were female. Among the HIV-infected group, 82 (53%) had a history of at least one C clinical category Centers for Diseases Control and Prevention event, and 134 (87%) were using combination antiretroviral therapy (cART). The median nadir CD4 percentage was 13% (0%–47%). 76(37.3%) experienced mild AEs. Seroconversion occurred in 46/154 (30%) of the HIV-infected group, and in 38/50 (76%) of the uninfected group (p<0.01). Factors associated with seroconversion in the HIV-infected group were: Never had a C clinical category event (OR=2.1, 95%CI=1.0–4.4); undetectable viral load at immunization (OR=2.4, 95%CI=1.1–5.2), and higher CD4 nadir/100 cells (OR=1.1, 95%CI=1.0–1.2). Conclusion MCC vaccine should be administered to HIV-infected children and adolescents after maximum immunologic and virologic benefit has been achieved with cART. Our data suggest that a single dose of MCC vaccine is insufficient for HIV-infected individuals 2–18 years of age.

Our findings suggest that higher CD4 T-cell activation leads to poor vaccine response in children living with HIV, which may be associated with a TReg/TInd disequilibrium.

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