title: Microbial TLR Agonists and Humoral Immunopathogenesis in HIV Disease.
abstract: Although T cells are the primary and most-studied targets of the Human Immunodeficiency Virus (HIV), B cells, especially memory B lymphocytes, are also chronically depleted in the course of HIV disease. Although the lack of CD4+T cell help may explain these deficiencies, intrinsic defects in B lymphocytes appear to contribute to B cell depletion and reduced antibody (Ab) production in the setting of HIV, especially of some antigens eliciting T cell-independent responses. The gut mucosal barrier is disrupted in HIV disease, resulting in increased systemic exposure to microbial products such as Toll-Like Receptor (TLR) agonists. The association of enhanced systemic levels of TLR agonists and B cell dysfunction in HIV disease is not understood. This review discusses the potential role of microbial TLR agonists in the B cell depletion, enhanced autoantibody production and impaired responses to vaccination observed in HIV-infected hosts. Increased microbial translocation in HIV infection may drive B cells to produce autoantibodies and increase susceptibilities of B cells to apoptosis through activation-induced cell death. Determining the mechanisms of B cell perturbations in HIV disease will inform the design of novel strategies of improve immune responses to vaccines, reduce opportunistic infections and slow disease progression.
authors.affiliation: Department of Medicine, Harvard Medical School, Boston, MA 02215, USA.
authors.forename: Xiaocong
authors.initials: X
authors.lastname: Yu
authors.affiliation: Department of Microbiology and Immunology, Department of Medicine, Division of Infectious Diseases, Medical University of South Carolina, BSB214E, Charleston, SC, 29425, USA.
authors.forename: Zihai
authors.initials: Z
authors.lastname: Li
authors.affiliation: NanJing Second Hospital, Infectious Diseases, NanJing, China.
authors.forename: Zhenxian
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: Department of Microbiology and Immunology, Department of Medicine, Division of Infectious Diseases, Medical University of South Carolina, BSB214E, Charleston, SC, 29425, USA.
authors.forename: J Michael
authors.initials: JM
authors.lastname: Kilby
authors.affiliation: Department of Microbiology and Immunology, Department of Medicine, Division of Infectious Diseases, Medical University of South Carolina, BSB214E, Charleston, SC, 29425, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Jiang
keywords: Antibody; Human Immunodeficiency Virus (HIV); Toll-like receptor