T-cell responses associated with resistance to Leishmania infection in individuals from endemic areas for Leishmania (Viannia) braziliensis

Abstract

Subclinical or asymptomatic infection is documented in individuals living in endemic areas for leishmaniasis suggesting that the development of an appropriate immune response can control parasite replication and maintain tissue integrity. A low morbidity indicates that intrinsic factors could favor resistance to Leishmania infection. Herein, leishmanial T-cell responses induced in subjects with low susceptibility to leishmaniasis as asymptomatic subjects were compared to those observed in cured cutaneous leishmaniasis (CCL) patients, who controlled the disease after antimonial therapy. All of them have shown maintenance of specific long-term immune responses characterized by expansion of higher proportions of CD4 + as compared to CD8 + Leishmania reactive T-lymphocytes. Asymptomatic subjects had lower indexes of in vitro Leishmania induced lymphoproliferative responses and interferon-gamma (IFN-γ) production in comparison to CCL patients. On the other hand, interleukin (IL-10) production was much higher in asymptomatics than in CCL, while no differences in IL-5 levels were found. In conclusion, long lived T-cell responses achieved by asymptomatic individuals differed from those who had developed symptomatic leishmaniasis in terms of intensity of lymphocyte activation (proliferation or IFN-γ) and regulatory mechanisms (IL-10). The absence of the disease in asymptomatics could be explained by their intrinsic ability to create a balance between immunoregulatory (IL-10) and effector cytokines (IFN-γ), leading to parasite destruction without producing skin tissue damage. The establishment of profiles of cell-mediated immune responses associated with resistance against Leishmania infection is likely to make new inroads into understanding the long-lived immune protection against the disease.Key words: asymptomatic infection -Leishmania (Viannia) braziliensis -cured leishmaniasis -cytokines -T-cell subsetslong term immunity (Grimaldi Jr & MacMahon-Pratt 1991). The spectrum of the clinical presentation ranges from self-healing or benign cutaneous lesions to more severe forms, such as disseminated lesions or mucosal involvement (Da-Cruz & Pirmez 2005).Studies conducted in mice and humans have unequivocally shown that a major T-cell driven component underlies the establishment of acquired immunity and protection against re-infection ( Coutinho et al. 1996, Louis et al. 1998, Bosque et al. 2000. Cytokines such as interferon-gamma (IFN-γ) and tumor necrosis factoralpha (TNF-α) activate macrophages for killing parasites, while interleukin (IL)-4, IL-5, IL-10, and transforming grow factor-beta (TGF-β) favor intracellular parasite growth (Louis et al. 1998. In addition, IL-10 production by CD4 + CD25 + T-cells is required for maintenance of Leishmania after cure, which in turn preserves an adaptive immunity to L. (Leishmania) major (Belkaid et al. 2002).The majority of ATL patients develop cutaneous leishmaniasis (CL) (Oliveira-Neto et al. 2000), but occurrence of subclinical or asymptomatic infection strongly suggests that po...

The Role of Inflammatory, Anti-Inflammatory, and Regulatory Cytokines in Patients Infected with Cutaneous Leishmaniasis in Amazonas State, Brazil

“…It has been demonstrated that the production of this cytokine by CD4 + CD25 T cells (Tregs) is associated with persistence of the parasite and reactivation of the disease [47–49]. IL-10 secretion by T H 1 cells likely is a mechanism that minimizes self-regulatory immunopathology of ACL [50, 51].…”

Laboratory Monitoring of Individuals with Subclinical Cutaneous Leishmaniasis Infections in Southern Brazil

“…Carvalho et al [23] found the agent of visceral leishmaniasis in healthy individuals who were residents of endemic areas of L. (L.) chagasi. The existence of a subclinical infection suggests the development of an appropriate immune response that can control the replication of the parasites and maintain tissue integrity (asymptomatic individuals produced more IL-10 than cured patients), hence the possibility of serologic study [24]. Although CL is endemic in several regions of Brazil, subclinical infections have been little studied, because the infection is difficult to investigate in individuals who do not exhibit clinical signs.…”

Local Delivery of the Toll-Like Receptor 9 Ligand CpG Downregulates Host Immune and Inflammatory Responses, Ameliorating Established Leishmania (Viannia) panamensis Chronic Infection

“…A hyperimmune (mixed Th1-Th2) response is associated with a more severe disease outcome in Leishmania (Viannia) infections (13,(37)(38)(39)(40)(63)(64)(65). Recently, it has been found in human L. (V.) panamensis infection that increased Treg capacity correlates with healing (18).…”

“…CpG activation of TLR9 has led to healing in experimental autoimmune diabetes (34) and amelioration of asthma and inflammatory arthritis through downregulation of Th2 cytokines (35,36). We therefore hypothesized, in light of recent results concerning the potential role of Tregs in leishmaniasis caused by L. (V.) panamensis infection and the role of inflammation in the pathology caused by L. (Viannia) parasites (37)(38)(39)(40), that CpG under the appropriate conditions could ameliorate pathology/disease.…”