Humoral immune responses to Streptococcus pneumoniae in the setting of HIV-1 infection

Abstract

Streptococcus pneumoniae (pneumococcus) remains one of the most commonly identified causes of bacterial infection in the general population, and the risk is 30-100 fold higher in HIV-infected individuals. Both innate and adaptive host immune responses to pneumococcal infection are important against pathogen invasion. Pneumococcal-specific IgA antibody (Ab) is key to control infection at the mucosal sites. Ab responses against pneumococcal infection by B cells can be generated through T cell-dependent or T cell-independent pathways. Depletion of CD4+ T cells is a hallmark of immunodeficiency in HIV infection and this defect also contributes to B cell dysfunction, which predisposes to infections such as the pneumococcus. Two pneumococcal vaccines have been demonstrated to have potential benefits for HIV-infected patients. One is a T cell dependent 13-valent pneumococcal conjugate vaccine (PCV13); the other is a T cell independent 23-valent pneumococcal polysaccharide vaccine (PPV23). However, many questions remain unknown regarding these two vaccines in the clinical setting in HIV disease. Here we review the latest research regarding B cell immune responses against pneumococcal antigens, whether derived from potentially invading pathogens or vaccinations, in the setting of HIV-1 infection.

Keywords: B cells; HIV; Humoral immune responses; Streptococcus pneumoniae.

Figure 1

Pulmonary infection due to Streptococcus pneumoniae in HIV-infected patients. HIV infection induces DCs and Tfh cells to secret cytokines such as type I interferon and IL-6 in the germinal center. HIV infection also attenuates the helper function of Tfh cells on B cells, which leads to the inhibition of humoral immune responses and decreased the production of antigen-specific IgA, IgG and IgM. Impaired memory B cells further facilitates S. pneumococcal uptake in AM. Meanwhile, pneumococcal infection stimulates AM to release inflammatory factors and chemokines, and recruit macrophages, neutrophils and CD4+ T cells, which also provides a favorable environment for HIV pathogenesis.