Opsonic Phagocytosis ofStreptococcus pneumoniaeby Alveolar Macrophages Is Not Impaired in Human Immunodeficiency Virus–Infected Malawian Adults

Abstract

Streptococcus pneumoniae is a major cause of pneumonia, bacteremia, and meningitis, especially among adults infected with the human immunodeficiency virus (HIV). Alveolar macrophages (AMs) are critical components of cellular defense against bacterial infection and are both infected and affected by HIV. In this study, AMs obtained at bronchoscopy from 44 Malawian adults (24 HIV positive and 20 HIV negative) were exposed in vitro to opsonized S. pneumoniae and coagulase-negative staphylococci. AMs from HIV-positive and -negative volunteers showed no significant difference in binding to or internalization of either S. pneumoniae or coagulase-negative staphylococci. In HIV-positive subjects, the presence of detectable HIV in lung fluid was not associated with AM impairment. AMs from HIV-infected adults did not exhibit impaired pneumococcal phagocytosis in the assay used. This suggests that an alternative mechanism of susceptibility is operating in these individuals.

The Alveolar Microenvironment of Patients Infected with Human Immunodeficiency Virus Does Not Modify Alveolar Macrophage Interactions with Streptococcus pneumoniae

“…We have previously observed normal opsonophagocytosis and killing of S. pneumoniae by alveolar macrophages obtained from patients with HIV infection (5). In this study, we extended that observation with new subjects and with the addition of a gamma interferon priming step.…”

“…Primed and mockprimed cells were challenged with opsonized type 1 S. pneumoniae on day 4. Immunofluorescence microscopy and killing assays were carried out as previously described (5).…”

“…Increased pneumococcal carriage (2), decreased CD4 ϩ lymphocyte function in the respiratory mucosa (3), impaired immunoglobulin function (4), and altered immunoglobulin responses to pneumococcal antigens have all been shown to play a role in the increased susceptibility to pneumococcal infection among HIV-infected subjects, but the importance of alveolar macrophage dysfunction remains unclear. Phagocytosis of pneumococci by alveolar macrophages was unimpaired in HIV-infected subjects (5), but limited studies of macrophage cytokine responses showed abnormalities potentially significant in neutrophil recruitment (6).…”

HIV-related lung disorders

“…The end result is a generalized state of cellular activation and accumulation of immune cells and pro-inflammatory mediators in the alveolar space. Interestingly, this does not appear to be due to defective alveolar macrophage phagocytic function as alveolar macrophages from HIV-infected subjects are not defective in their ability to ingest pneumococcus opsonized with pooled IgG [8], mycobacteria [9], or Cryptococcus [10]. This could reflect chronic macrophage activation in HIV-infected subjects due to persistent levels of interferon-gamma (IFN-γ) in the alveolar space [9,11,12].…”

Macrophages Are Phenotypically and Functionally Diverse across Tissues in Simian Immunodeficiency Virus-Infected and Uninfected Asian Macaques

“…Aberrations in immunological responses are not limited to a loss of CD4 ϩ T cells and extend to inappropriate lymphocyte priming, proliferation, and functional exhaustion and dysfunctional antigen presentation and cytokine secretion by dendritic cells (DCs) (7,8). Despite the welldocumented roles of macrophages in mitigating the translocation of microbial products and in orchestrating appropriate immune responses, a comprehensive understanding of the contributions of tissue-resident macrophages to HIV and SIV disease progression is lacking, with some studies suggesting functional abnormalities within myeloid cells of HIV-infected humans or SIV-infected macaques (9)(10)(11)(12)(13)(14)(15).…”