HIV gp120 in Lungs of ART-Treated Individuals Impairs Alveolar Macrophage Responses To Pneumococci

Rationale: People living with HIV are at significantly increased risk of invasive pneumococcal disease, despite long-term antiretroviral therapy (ART). The mechanism explaining this observation remains undefined.Objectives: To determine if apoptosis-associated microbicidal mechanisms, required to clear intracellular pneumococci that survive initial phagolysosomal killing, are perturbed.Methods: Alveolar macrophages (AM) were obtained by BAL from healthy donors or HIV-1–seropositive donors on long-term ART with undetectable plasma viral load. Monocyte-derived macrophages (MDM) were obtained from healthy donors and infected with HIV-1BaL or treated with gp120. Macrophages were challenged with opsonized serotype 2 Streptococcus pneumoniae and assessed for apoptosis, bactericidal activity, protein expression, and mitochondrial reactive oxygen species (mROS). AM phenotyping, ultrasensitive HIV-1 RNA quantification, and gp120 measurement were also performed in BAL.Measurements and Main Results: HIV-1BaL infecti...