High levels of T lymphocyte activation in Leishmania-HIV-1 co-infected individuals despite low HIV viral load

<p>Abstract</p> <p>Background</p> <p>Concomitant infections may influence HIV progression by causing chronic activation leading to decline in T-cell function. In the Americas, visceral (AVL) and tegumentary leishmaniasis (ATL) have emerged as important opportunistic infections in HIV-AIDS patients and both of those diseases have been implicated as potentially important co-factors in disease progression. We investigated whether leishmaniasis increases lymphocyte activation in HIV-1 co-infected patients. This might contribute to impaired cellular immune function.</p> <p>Methods</p> <p>To address this issue we analyzed CD4⁺T absolute counts and the proportion of CD8⁺T cells expressing CD38 in <it>Leishmania</it>/HIV co-infected patients that recovered after anti-leishmanial therapy.</p> <p>Results</p> <p>We found that, despite clinical remission of leishmaniasis, AVL co-infected patients presented a more severe immunossupression as suggested by CD4⁺T cell counts under 200 cells/mm³, differing from ATL/HIV-AIDS cases that tends to show higher lymphocytes levels (over 350 cells/mm³). Furthermore, five out of nine, AVL/HIV-AIDS presented low CD4⁺T cell counts in spite of low or undetectable viral load. Expression of CD38 on CD8⁺T lymphocytes was significantly higher in AVL or ATL/HIV-AIDS cases compared to HIV/AIDS patients without leishmaniasis or healthy subjects.</p> <p>Conclusions</p> <p><it>Leishmania </it>infection can increase the degree of immune system activation in individuals concomitantly infected with HIV. In addition, AVL/HIV-AIDS patients can present low CD4⁺T cell counts and higher proportion of activated T lymphocytes even when HIV viral load is suppressed under HAART. This fact can cause a misinterpretation of these laboratorial markers in co-infected patients.</p

Microbial Translocation Induces an Intense Proinflammatory Response in PatientsWith Visceral Leishmaniasis and HIV Type 1 Coinfection

Made available in DSpace on 2015-08-19T13:49:27Z (GMT). No. of bitstreams: 2 license.txt: 1914 bytes, checksum: 7d48279ffeed55da8dfe2f8e81f3b81f (MD5) carmen_grippetal_IOC_2013.pdf: 1114513 bytes, checksum: 1f42f1059dc7ace46b709ed310bae90c (MD5) Previous issue date: 2013Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório Interdisciplinar de Pesquisas Médicas. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa sobre o Timo. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de AIDS e Imunologia Molecular. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio Grande do Norte. Departamento de Bioquímica. Natal, RN, Brasil.Universidade Federal do Mato Grosso do Sul. Hospital Universitário. 7Hospital-Dia Profa Esterina Corsini. Campo Grande, MS, Brasil.Universidade de São Paulo. Instituto de Medicina Tropical de São Paulo. São Paulo, SP, Brasil.Universidade de São Paulo. Instituto de Medicina Tropical de São Paulo. São Paulo, SP, Brasil.Fundação Oswaldo Cruz. Instituto de Pesquisa Clínica Evandro Chagas (IPEC). Rio de Janeiro, RJ, Brasil.Fundação de Medicina Tropical Dr. Heitor Vieira Dourado. Manaus, AM, BrasilFundação Oswaldo Cruz. Instituto de Pesquisa Clínica Evandro Chagas (IPEC). Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio Grande do Norte. Departamento de Bioquímica. Natal, RN, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de AIDS e Imunologia Molecular. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório Interdisciplinar de Pesquisas Médicas. Rio de Janeiro, RJ, Brasil / Universidade do Estado do Rio de Janeiro, Faculdade de Ciências Médicas. Disciplina de Parasitologia. Rio de Janeiro, RJ, Brasil.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