Abstract
Pneumococcal disease is associated with a particularly high morbidity and mortality amongst adults in HIV endemic countries. Our previous findings implicating a B-cell defect in HIV-infected children from the same population led us to comprehensively characterize B-cell subsets in minimally symptomatic HIV-infected Malawian adults and investigate the isotype-switched IgG memory B-cell immune response to the pneumococcus. We show that similar to vertically acquired HIV-infected Malawian children, horizontally acquired HIV infection in these adults is associated with IgM memory B-cell (CD19+ CD27+ IgM+ IgD+) depletion, B-cell activation and impairment of specific IgG B-cell memory to a range of pneumococcal proteins. Our data suggest that HIV infection affects both T-cell independent and T-cell dependent B-cell maturation, potentially leading to impairment of humoral responses to extracellular pathogens such as the pneumococcus, and thus leaving this population susceptible to invasive disease.
Highlights
The burden of invasive pneumococcal disease (IPD) is high in many African countries, including Malawi, where a high prevalence of HIV infection is associated with increased rates and severity of IPD in both adults and children [1,2,3]
In Malawian children, we have previously demonstrated a shift in the B-cell compartment toward an apoptosis-prone phenotype (CD19+ CD102 CD21lo) evident early in HIV disease progression, associated with reduced numbers of pneumococcal protein antigen–specific memory B-cells [5] which may in part explain their susceptibility to IPD
Taken together these data suggest that in minimally symptomatic HIV-infected individuals, the B-cell compartment is profoundly disrupted with a considerable shift in the distribution of normal B-cell subsets in the blood
Summary
The burden of invasive pneumococcal disease (IPD) is high in many African countries, including Malawi, where a high prevalence of HIV infection is associated with increased rates and severity of IPD in both adults and children [1,2,3]. The mature activated B-cells have increased expression of CD95 and are notably susceptible to CD95 ligand-mediated apoptosis, while the immature transitional B-cells are notably susceptible to intrinsic apoptosis, expressing very low levels of anti-apoptotic Bcl-2 proteins [8,9,10,11]. It is uncertain, whether these Bcell defects occur in African adults or whether they impact on antigen-specific immunity. We comprehensively characterized the B-cell subset profile of HIV-infected Malawian adults and investigated whether the dysregulation identified was associated with loss of isotype-switched IgG memory B-cells to pneumococcal protein antigens
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