title: Microbial translocation induces an intense proinflammatory response in patients with visceral leishmaniasis and HIV type 1 coinfection.
abstract: BACKGROUND
  Leishmania infection is a cofactor in the heightened cellular activation observed in patients with American visceral leishmaniasis and human immunodeficiency virus type 1 (HIV) infection, with or without progression to AIDS (AVL/HIV). Thus, the persistence of a high parasite load despite antileishmanial therapy could be responsible for the continued immune stimulation.
  
  
  METHODS
  CD8(+) T cells expressing CD38, parasite load, lipopolysaccharide (LPS), soluble CD14, macrophage migration inhibitory factor (MIF), intestinal fatty acid-binding protein (IFABP), and proinflammatory cytokines (interleukin 1β, interleukin 6, interleukin 8, interleukin 17, interferon γ, and tumor necrosis factor) were measured in 17 patients with AVL/HIV, 16 with HIV, and 14 healthy subjects (HS).
  
  
  RESULTS
  Lower Leishmania parasitemia was observed after antileishmanial and antiretroviral therapies. However, higher levels of CD38(+) on CD8(+) T cells were observed in both clinical phases of leishmaniasis, compared with HIV cases. AVL/HIV and HIV patients showed higher levels of LPS and IFABP than HS. Proinflammatory cytokine levels were significantly augmented in patients with active coinfection, as well as those with remission of Leishmania infection. LPS levels and Leishmania infection were positively correlated with CD38 expression on CD8(+) T cells and with IL-6 and IL-8 levels.
  
  
  CONCLUSIONS
  LPS levels along with the immune consequences of Leishmania infection were associated with elevated cellular activation in coinfected patients. As a consequence, secondary chemoprophylaxis for leishmaniasis or even the use of antiinflammatory drugs or antibiotics may be considered for improving the prognosis of AVL/HIV.
authors.affiliation: Laboratório Interdisciplinar de Pesquisas Médicas, Instituto Oswaldo Cruz, FIOCRUZ, Av. Brasil 4365, Manguinhos, Rio de Janeiro-RJ, Brazil.
authors.forename: Joanna R
authors.initials: JR
authors.lastname: Santos-Oliveira
authors.forename: Eduardo G
authors.initials: EG
authors.lastname: Regis
authors.forename: Carmem B W
authors.initials: CB
authors.lastname: Giacoia-Gripp
authors.forename: Joanna G
authors.initials: JG
authors.lastname: Valverde
authors.forename: Priscilla
authors.initials: P
authors.lastname: Alexandrino-de-Oliveira
authors.forename: Jose Ângelo L
authors.initials: JÂ
authors.lastname: Lindoso
authors.forename: Hiro
authors.initials: H
authors.lastname: Goto
authors.forename: Manoel P
authors.initials: MP
authors.lastname: Oliveira-Neto
authors.forename: Jorge O
authors.initials: JO
authors.lastname: Guerra
authors.forename: Beatriz
authors.initials: B
authors.lastname: Grinsztejn
authors.forename: Selma B
authors.initials: SB
authors.lastname: Jerônimo
authors.forename: Mariza G
authors.initials: MG
authors.lastname: Morgado
authors.forename: Alda M
authors.initials: AM
authors.lastname: Da-Cruz
mesh_terms: D019380:Anti-HIV Agents / Q000627:therapeutic use; D060085:Coinfection / Q000188:drug therapy / Q000276:immunology / Q000469:parasitology / Q000821:virology; D003430:Cross-Sectional Studies; D050556:Fatty Acid-Binding Proteins / Q000097:blood; D015658:HIV Infections / Q000150:complications* / Q000276:immunology; D015497:HIV-1 / Q000276:immunology; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D016209:Interleukin-8 / Q000097:blood; D007898:Leishmaniasis, Visceral / Q000150:complications* / Q000188:drug therapy / Q000276:immunology; D018950:Lipopolysaccharide Receptors / Q000097:blood; D008070:Lipopolysaccharides / Q000097:blood; D018512:Parasitemia / Q000276:immunology / Q000469:parasitology / Q000821:virology; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D019380:Anti-HIV Agents; D050556:Fatty Acid-Binding Proteins; D015850:Interleukin-6; D016209:Interleukin-8; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides
keywords: inflammatory cytokines; microbial translocation; visceral leishmaniasis-HIV/AIDS coinfection