title: Lipopolysaccharide-Induced Cellular Activation May Participate in the Immunopathogenesis of Visceral Leishmaniasis Alone or in HIV Coinfection.
abstract: Visceral Leishmaniasis (VL) is an infectious disease which constitutes a serious public health problem, integrating the list of neglected tropical diseases. The disease is characterized by a Leishmania-specific immune suppression T-cell depletion and a decrease of other hematopoietic cells. In parallel, an immunostimulatory response also occurs, represented by polyclonal B lymphocytes, T-cell activation, and systemic proinflammatory responses. Parasite antigens were believed to mediate both suppression and activation mechanisms, but these concepts are constantly being revised. Similar to reports on HIV/AIDS, we have proposed that gut parasitation by amastigotes and lymphocyte depletion could also affect gut-associated lymphoid tissue, leading to mucosal barrier breach and predisposing to microbial translocation. An increment of plasmatic lipopolysaccharide (LPS) levels observed in Brazilian VL patients was implicated in the reduced blood CD4(+) and CD8(+) T cell counts, systemic T-cell activation, pro-inflammatory cytokines and MIF plasma levels, suggesting that a bacterial molecule not associated with Leishmania infection can exert deleterious effects on immune system. Recent results also pointed that the proinflammatory response was potentiated in VL/HIV-AIDS coinfected patients. The LPS-mediated cell activation adds another concept to the immunopathogenesis of VL and can bring a rational for new therapeutic interventions that could ameliorate the management of these patients.
authors.affiliation: Laboratório Interdisciplinar de Pesquisas Médicas, Instituto Oswaldo Cruz, FIOCRUZ, 21040-360 Rio de Janeiro, RJ, Brazil.
authors.forename: Joanna Reis
authors.initials: JR
authors.lastname: Santos-Oliveira
authors.forename: Alda Maria
authors.initials: AM
authors.lastname: Da-Cruz