Systemic antibody responses to gut commensal bacteria during chronic HIV-1 infection

Abstract

BACKGROUND: Human systemic antibody responses to commensal microbiota are not well characterised during health and disease. Of particular interest is the analysis of their potential modulation caused by chronic HIV-1 infection which is associated with sustained enteropathy and systemic B cell disturbances reflected by impaired B cell responses and chronic B cell hyperactivity. The mechanisms underlying B cell hyperactivation and the specificities of the resulting hypergammaglobulinaemia are only poorly understood. METHODS: By a technique referred to as live bacterial FACS (fluorescenceactivated cell sorting), the present study investigated systemic antibody responses to several gut and skin commensal bacteria as well as Candida albicans in longitudinal plasma and serum samples from healthy donors, chronic HIV-1-infected individuals with or without diarrhoea and patients with inflammatory bowel disease (IBD). RESULTS: The data show that systemic antibody responses to the commensal microbiota were abundantly present in humans and remained remarkably stable over years. Overall systemic antibody responses to gut commensal bacteria were not affected during chronic HIV-1 infection, with titres decreasing when normalised to elevated plasma immunoglobulin G (IgG) levels found in patients with HIV. In contrast, increases in the titres of high affinity antimicrobiota antibodies were detected in patients with IBD, demonstrating that conditions with known increased intestinal permeability and aberrant mutualism can induce changes in antibody titres observed in these assays. CONCLUSION: Neither HIV-associated enteropathy nor B cell dysfunction impact on the high-affinity systemic antibody responses to gut commensal bacteria. HIV-associated hypergammaglobulinaemia is therefore unlikely to be driven by induction of antimicrobiota antibodies. Systemic antibody responses to gut commensal bacteria during chronic HIV-1 infection

Candida and candidiasis in HIV-infected patients

“…Their levels and specificity do not seem to change during HIV infection and the associated B-cell activation and hypergammaglobulinemia [67]. Although most dominant antibodies appear to be ineffective for protection against oral disease, or could even enhance the disorder by deviating a protective host response, some protective specificities and isotypes have been reported.…”

Antigen-Dependent and -Independent Mechanisms of T and B Cell Hyperactivation during Chronic HIV-1 Infection

“…Indeed, HIV-associated B cell disturbances have been observed not only systemically but also locally in the HIV-infected gut, evidenced by intestinal B cell hyperactivity, destruction of gastrointestinal germinal centers, and intrafollicular impairment of the immunoglobulin switch enzyme activationinduced deaminase (AID) (91,111,155). Whether HIV-associated enteropathy and increased systemic exposure to GI tract microbial antigens contribute to HIV-associated hypergammaglobulinemia in an antigen-dependent manner was recently addressed (60). In that study, systemic antibody responses to a selection of GI tract commensals in patients with early or advanced HIV infection were assessed, as were those in patients suffering from inflammatory bowel disease (IBD).…”

“…It is therefore conceivable that antibody responses with specificity for persistent/latent coinfecting viruses might contribute to hypergammaglobulinemia in HIV-1 infection. Indeed, despite the fact that antibody responses to novel antigens and booster vaccines such as tetanus toxoid are impaired during chronic HIV-1 infection (60,64,98,104,105,117), CMV IgG levels are equally high or even higher in HIV-infected individuals than in healthy donors in the absence of overt CMV reactivation (46,60,120). However, these variable increases in CMV-specific IgG titers in HIV-infected individuals cannot account for the extent of hypergammaglobulinemia observed in these patients, lending further support to a strong component of antigen-unspecific hyperactivation of B cells during untreated HIV-1 infection.…”

Role of Antilipopolysaccharide Antibodies in Serum Bactericidal Activity against Salmonella enterica Serovar Typhimurium in Healthy Adults and Children in the United States

“…Exposure and immunological sensitization to LPS is thus likely to be a characteristic of most populations. Indeed, serum IgM, IgA, and IgG antibodies to surface antigens of a number of different gut commensal bacteria have been observed in healthy individuals (31). Taking these facts into consideration, it seems plausible that the bactericidal antibodies detected in our study represent a response to some source of LPS present in either the external or the internal (commensal) environment and that these antibodies fortuitously cross-react with S. Typhimurium LPS.…”