Epidemiologic and Immunologic Findings for the Subclinical Form of<i>Leishmania braziliensis</i>Infection

Follador, Ivonise; Araújo, Claudio Gil; Bacellar, Olı́via; Clarissa, B. Araújo; Lucas, Peter C.; Roque, P. Almeida; Edgar, M. Carvalho

doi:10.1086/340261

Cited by 103 publications

(112 citation statements)

References 23 publications

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“…On the other hand, the occurrence of subclinical infection or asymptomatic individuals in endemic areas suggests that infected individuals can control Leishmania replication preventing the development of the disease. In this connection, the maintenance of Leishmania specific long-term immunity in asymptomatic subjects reinforces the idea that frequent parasite stimuli can confer protection against Leishmania re-infection or reactivation in individuals from endemic areas (Bosque et al 2000, Follador et al 2002.In asymptomatic individuals low levels of IFN-γ and TNF-α are induced contrasting with the strong production of these cytokines observed during active leishmaniasis (Follador et al 2002). It should be pointed out that enough amounts of inflammatory cytokines can be sufficient to control parasite infection, but regulatory mechanisms underlying resistance against leishmaniasis need to be better clarified.…”

supporting

confidence: 61%

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

Bittar

Nogueira

Vieira-Gonçalves

et al. 2007

Mem. Inst. Oswaldo Cruz

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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...

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supporting

confidence: 61%

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

Bittar

Nogueira

Vieira-Gonçalves

et al. 2007

Mem. Inst. Oswaldo Cruz

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“…The immune response of the New World LCL caused by L. braziliensis, is characterized by a Th1 response, with a predominance of IFN-gamma expression in vitro and in situ and a very low or sometimes absent expression of IL-4, IL-5 and IL-10 1,2,5, [11][12][13][14][15]20 . In relation to other cytokines, such as IL-2, they have been demonstrated in vitro and in situ, with a low expression.…”

Section: Discussionmentioning

confidence: 99%

“…Differently, in this context, cytokines may play different roles in the pathogenesis, being more related to the maintenance of the inflammatory reaction in the tissue. Studies in this context have identified both Th1 and Th2-type cytokines in Leishmania antigen-stimulated peripheral blood mononuclear cell supernatant in LCL 11,13,15 and also in MCL 13 . PCR studies of lesion samples have shown Th1 profile LCL and both Th1 and Th2 in MCL 26 .…”

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confidence: 99%

Cytokine profile in Montenegro skin test of patients with localized cutaneous and mucocutaneous leishmaniasis

Nogueira

Goto

Sotto

et al. 2008

Rev. Inst. Med. trop. S. Paulo

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SuMMarYAmerican tegumentary leishmaniasis presents as two major clinical forms: localized cutaneous leishmaniasis (LCL) and mucocutaneous leishmaniasis (MCL). The immune response in leishmaniasis is efficiently evaluated by the response to Leishmania antigen through the Montenegro skin test (MST). Both LCL and MCL present positive response to MST, indicating that the patients present cell-mediated immunity against the parasite -Leishmania. In spite of the presence of immunity in MCL, this is not sufficient to stop disease progression and prevent resistance to treatment. In this study we demonstrated interleukin (IL) 2, 4, 5 and interferon (IFN) gamma expression in biopsies of MST of ten patients with American tegumentary leishmaniasis. The obtained results were compared between LCL (n = 5) and MCL (n = 5) patients. The MST of MCL patients displayed a higher expression of IL-2, IL-4 and IL-5, in comparison to LCL. There was no significant difference in IFN-gamma expression between groups. The obtained results suggest the role of IL-4 and IL-5 in the maintenance of the immunopathogenic mechanism of the destructive lesions that characterize MCL.

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“…The traditional clinical manifestations are single or multiple cutaneous lesions, but L. (V.) braziliensis has also been associated with mucosal or mucocutaneous leishmaniasis (Marzochi & Marzochi 1994). Nevertheless, most infected individuals remain asymptomatic indefinitely, and show a cell-mediated or humoral immune response to Leishmania antigens or parasites in peripheral blood detected by polymerase chain reaction (PCR) (Follador et al 2002, de Oliveira Camera et al 2006.…”

mentioning

confidence: 99%

First encounter of subclinical human Leishmania (Viannia) infection in State of Rio Grande do Sul, Brazil

Fagundes

Marzochi

Fernandes³

et al. 2007

Mem. Inst. Oswaldo Cruz

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Epidemiologic and Immunologic Findings for the Subclinical Form ofLeishmania braziliensisInfection

Cited by 103 publications

References 23 publications

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

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

Cytokine profile in Montenegro skin test of patients with localized cutaneous and mucocutaneous leishmaniasis

First encounter of subclinical human Leishmania (Viannia) infection in State of Rio Grande do Sul, Brazil

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