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

Abstract

BackgroundConcomitant 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.MethodsTo address this issue we analyzed CD4+ T absolute counts and the proportion of CD8+ T cells expressing CD38 in Leishmania/HIV co-infected patients that recovered after anti-leishmanial therapy.ResultsWe 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.ConclusionsLeishmania 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.

Visceral Leishmaniasis and HIV Coinfection in Latin America

“…Consistently, increased percentages of molecules associated with T cell activation, such as CD38 on CD8 + T cells and HLA-DR, are observed in VL/HIV patients compared to HIV/AIDS cases alone, and these molecules do not reach normal values despite undetectable viral load and clinical remission of leishmaniasis [46]. These molecules, especially those related to the risk of reactivation [47], also increase during VL relapse, suggesting that such molecules could be predictive of clinical outcome.…”

“…One patient presented confluent, miliary papules on the face, thorax, and limbs, and the other presented non-pruritic and erythematous maculopapular lesions on the face and thorax [64], [65]. In two other patients [46], [66], the cutaneous lesion was concomitant to visceral involvement (erythematous papules and plaques). In one of these patients, the strain of Leishmania involved in the cutaneous lesions was L. donovani , which was confirmed by DNA sequence analysis [46].…”

Enhanced T cell activation in Plasmodium falciparum malaria-infected human immunodeficiency virus-1 patients from Mozambique

“…Similar to that observed for the CD4 + T counts, the viral or parasite antigens appear to act together to boost cell activation, either directly or by inducing the release of soluble factors. HIV-1 co-infection with other diseases, such as leishmaniasis (Santos-Oliveira et al 2010), tuberculosis (Rodrigues et al 2003) or leprosy (Giacoia-Gripp et al 2011), has previously been demonstrated to increase cellular activation. A previous study conducted in Mz did not identify a significant correlation between the "malaria infection" parameter and the levels of HLA-DR/CD38 on activated CD4 + and CD8 + T cells (Naniche et al 2011).…”

Immunopathogenesis of non-healing American cutaneous leishmaniasis and progressive visceral leishmaniasis

“…Co-infection studies in primary human monocyte-derived MΦs, DCs, and tonsillar tissue demonstrated that each pathogen has a detrimental effect on containment of the other— Leishmania infection enhances HIV replication via chronic immune activation, and that HIV promotes Leishmania infection by suppressing a protective host defense [109–112]. The latter is corroborated by higher levels of L. donovani parasitemia in HIV co-infected individuals [113] and low CD4 + T cell counts despite suppression of viral load by antiretroviral therapy [114]. …”