Comparison of the Immune Profile of Nonhealing Cutaneous Leishmaniasis Patients with Those with Active Lesions and Those Who Have Recovered from Infection

Abstract

Th1-type cellular immune responses play a critical role in protection against infection with Leishmania parasites, whereas activation of Th2-type cells results in progressive disease. Cutaneous leishmaniasis caused by Leishmania major is often a self-healing disease; however, persistent nonhealing forms are also known. In the present study, we have described cell-mediated immune responses in nonhealing patients by measuring T-cell proliferation, cytokine production, and phenotypic characterization of these cells. The responses were compared with those of patients with active lesions, patients who had recovered from infection, and healthy controls. Peripheral blood mononuclear cells from patients with active lesions and recovered donors proliferated vigorously and produced Th1-type cytokine when stimulated with L. major antigens, whereas in nonhealing patients the proliferative responses were significantly lower and showed a Th2-type response to Leishmania antigens. Interleukin-10 (IL-10) production was not a feature of L. major stimulation. Flow cytometric analysis revealed that L. major antigen induced proliferation of the CD4-positive population and that these cells were the major source of gamma interferon and IL-4. These results show a distinct dichotomy in the cytokine response to L. major infection.Leishmania major is the causative agent of zoonotic cutaneous leishmaniasis (CL) and affects millions of people in many parts of the world (30). The disease is prevalent in many areas of Iran. Hyperendemic foci of zoonotic CL in northeastern, southwestern, and central parts of Iran have been reported (9, 10, 31). The most common presentation of CL is one or a few skin lesions, which often heal spontaneously and leave a depressive scar. However, a rare presentation of infection, involving persistent lesions, is also known. These so-called nonhealing forms last for several years and do not respond to conventional chemotherapies. Patients are mostly from areas of hyperendemic infection and include some of the soldiers who were immunized with virulent parasites (leishmanization) during the Iraq war against Iran. Some of these patients experience periods of remission and reactivation at the site of inoculation, and others suffer from chronic lesion for several years.Extensive studies with experimental models have shown that the outcome of infection is critically dependent on the activation of one of the two subsets of CD4 T cells, Th1 and Th2 (26). Gamma interferon (IFN-␥), secreted by Th1 cells, is the most potent macrophage-activating cytokine leading to host resistance to infection with Leishmania parasites (27, 29), whereas interleukin-4 (IL-4), secreted by Th2 cells, is associated with down-modulation of IFN-␥-mediated macrophage activation (1, 17). However, in human cutaneous leishmaniasis, a clear functional dichotomy in CD4 T cells has not definitely been documented. Concerning the key role of cytokines, we were interested in defining the immune response of nonhealing patients and comparing it with that of in...

Aspectos sorológicos e epidemiológicos da leishmaniose tegumentar americana canina em Maricá, Rio de Janeiro, Brasil

“…A resposta tipo 2 gera aumento de IL4, que estimula a diferenciação de linfócitos B, ocasionado aumento na produção de anticorpos. Este padrão encontra-se associado comumente a pacientes com doença severa 1 . A utilização da resposta humoral no diagnóstico da infecção tegumentar, portanto, permanece controverso pela baixa quantidade de anticorpos séricos detectáveis pelos métodos tradicionais e pela infinidade de reações cruzadas observadas principalmente nas técnicas imunoenzimáticas devido a sua sensibilidade acentuada.…”

Immunological and Genetic Evidence for a Crucial Role of IL-10 in Cutaneous Lesions in Humans Infected with Leishmania braziliensis

“…Nonhealing lesions in humans infected with L. major, have been associated with low levels of IFN-␥ and high levels of IL-4 and, in contrast, healing lesions were associated with elevated levels of IFN-␥ and low levels of IL-4 (18) in PBMCs. IFN-␥, IL-1, IL12p40, TNF-␣, TGF-␤, and IL-10 mRNA were detected in the lesions of healing subjects, whereas IL-4 mRNA was only found in a few biopsies (19); in these cases, lesion healing was again associated with elevated levels of IFN-␥ and low levels of IL-4.…”

Childhood cutaneous leishmaniasis: report of 117 cases from Iran

“…Phlebotomus longipes can not bite over the clothing, but bite the exposed areas of the body to suck the blood, so the lesions mainly appear in hands, face and legs (Nadim and Seyedi, 1971). Considering the fact that about 48.7% of patients had one or more skin lesions, we concluded that a sandfly, because of its physiologic characteristics, bites the host more than one time, and from every area of the bite, parasites enter the blood (Ahmadiyazdi et al, 2004;Yaghoobi et al, 2002;Ajdary et al, 2000).…”