Leishmania Chagasi Antigens Recognized in Cured Visceral Leishmaniasis and Asymptomatic Infection

Ac, White; Castes, M; García, Lucila; Trujillo, Dinorah; Zambrano, Luz Belén

doi:10.4269/ajtmh.1992.46.123

Cited by 31 publications

(27 citation statements)

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“…Thus, individuals who control parasite burden successfully either following treatment in the case of patients or due to adequate immunity, as in endemic contacts, exhibit good T cell reactivity to the Leishmania Ag. The presence of a positive immune response in all of the five endemic contacts suggests that the frequency of subclinical infection in an endemic area such as Bihar is high, as has been reported in other areas of the world (38)(39)(40). The majority of people infected with L. chagasi or L. donovani have been shown to clear their infection spontaneously and develop protective immunity, characterized by lymphocyte proliferation and secretion of IFN-g in response to Ag in vitro.…”

Section: Discussionmentioning

confidence: 87%

Elongation Factor-2, a Th1 Stimulatory Protein of Leishmania donovani, Generates Strong IFN-γ and IL-12 Response in Cured Leishmania-Infected Patients/Hamsters and Protects Hamsters against Leishmania Challenge

Kushawaha

Gupta

Sundar

et al. 2011

The Journal of Immunology

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In visceral leishmaniasis, Th1 types of immune responses correlate with recovery from and resistance to disease, and resolution of infection results in lifelong immunity against the disease. Leishmanial Ags that elicit proliferative and cytokine responses in PBMCs from cured/exposed/Leishmania patients have been characterized through proteomic approaches, and elongation factor-2 is identified as one of the potent immunostimulatory proteins. In this study, we report the cloning and expression of Leishmania donovani elongation factor-2 protein (LelF-2) and its immunogenicity in PBMCs of cured/exposed Leishmania-infected patients and hamsters (Mesocricetus auratus). Leishmania-infected cured/exposed patients and hamsters exhibited significantly higher proliferative responses to recombinant Lelf-2 (rLelF-2) than those with L. donovani-infected hosts. The soluble L. donovani Ag stimulated PBMCs of cured/exposed and Leishmania patients to produce a mixed Thl/Th2-type cytokine profile, whereas rLelF-2 stimulated the production of IFN-γ, IL-12, and TNF-α but not IL-4 or IL-10. Further, rLelF-2 downregulated LPS-induced IL-10 as well as soluble L. donovani Ag-induced IL-4 production by Leishmania patient PBMCs. The immunogenicity of rLelF-2 was also checked in hamsters in which rLelF-2 generates strong IL-12– and IFN-γ–mediated Th1 immune response. This was further supported by a remarkable increase in IgG2 Ab level. We further demonstrated that rLelF-2 was able to provide considerable protection (∼65%) to hamsters against L. donovani challenge. The efficacy was supported by the increased inducible NO synthase mRNA transcript and Th1-type cytokines IFN-γ, IL-12, and TNF-α and downregulation of IL-4, IL-10, and TGF-β. Hence, it is inferred that rLelF-2 elicits a Th1 type of immune response exclusively and confers considerable protection against experimental visceral leishmaniasis.

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Section: Discussionmentioning

confidence: 87%

Elongation Factor-2, a Th1 Stimulatory Protein of Leishmania donovani, Generates Strong IFN-γ and IL-12 Response in Cured Leishmania-Infected Patients/Hamsters and Protects Hamsters against Leishmania Challenge

Kushawaha

Gupta

Sundar

et al. 2011

The Journal of Immunology

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“…It has often been used as a correlate of immunity in vaccine trials (42) and is considered predictive of successful chemotherapy in visceral leishmaniasis (43). In mice, rechallenge of healed L. major-infected mice results in the development of a strong tuberculoid-type DTH response (44) that is mediated by CD4 ϩ T cells (45).…”

Section: Discussionmentioning

confidence: 99%

Th1 Cell-Mediated Resistance to Cutaneous Infection with Leishmania major Is Independent of P- and E-Selectins

Zaph

Scott

2003

The Journal of Immunology

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Studies in several models of inflammation have underscored the importance of P- and E-selectins in the migration of T cells to inflamed tissues. However, the role of the endothelial selectins in infection-induced cutaneous inflammation and host-protective immunity has not been investigated. In this study, we demonstrate that CD4+ T cells recruited to the cutaneous compartment during infection with Leishmania major express P- and E-selectin ligands. Furthermore, expression of P- and E-selectin ligands correlates with activated Leishmania-specific Th1 cells and is dependent upon IL-12. To investigate the functional role of the endothelial selectins during leishmaniasis, we infected mice either singly or doubly deficient in the expression of P- and E- selectins. Mice lacking both P- and E-selectins developed significantly less inflammation at the site of a primary and secondary infection, and exhibited an impaired delayed-type hypersensitivity response. Surprisingly, the absence of the endothelial selectins had no effect on the control of parasite replication or immunity to reinfection. Thus, these data demonstrate that although the endothelial selectins contribute to the inflammatory response, they are not required for protective immunity to L. major. Moreover, these data suggest that by blocking P- and E-selectins, the immune pathology associated with cutaneous leishmaniasis might be ameliorated without compromising immunity to infection.

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“…Cured or subclinical individuals are able to mount antigenspecific IFN-␥ responses following Leishmania antigen restimulation in vitro. Cured patients are also resistant to reinfection and are leishmanin skin test positive, suggesting no inherent defect in the antigen-dependent T H 1 response (3,7,34).…”

mentioning

confidence: 99%

“…Treated individuals develop a cell-mediated immune response capable of offering protection from reinfection, as characterized by antigen-specific IFN-␥ responses (7,34). In contrast, individuals with advanced VL show a decrease in antigen-specific IFN-␥ production and elevated levels of the immunoregulatory cytokine IL-10 in serum and increased IL-10 mRNA expression in lesional tissue (6,10).…”

mentioning

confidence: 99%

Immunologic Indicators of Clinical Progression during CanineLeishmania infantumInfection

Boggiatto

Ramer‐Tait

Metz

et al. 2010

Clin Vaccine Immunol

104

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In both dogs and humans Leishmania infantum infection is more prevalent than disease, as infection often does not equate with clinical disease. Previous studies additively indicate that advanced clinical visceral leishmaniasis is characterized by increased production of anti-Leishmania antibodies, Leishmania-specific lymphoproliferative unresponsiveness, and decreased production of gamma interferon (IFN-␥) with a concomitant increase of interleukin-10 (IL-10). In order to differentiate infection versus progressive disease for better disease prognostication, we temporally evaluated humoral and cellular immunologic parameters of naturally infected dogs. The work presented here describes for the first time the temporal immune response to natural autochthonous L. infantum infection in foxhounds within the United States. Several key changes in immunological parameters should be considered when differentiating infection versus clinical disease, including a dramatic rise in IgG production, progressive increases in antigen-specific peripheral blood mononuclear cell proliferation, and IFN-␥ production. Polysymptomatic disease is precluded by increased IL-10 production and consistent detection of parasite kinetoplast DNA in whole blood. This clinical presentation and the immuno-dysregulation mirror those observed in human patients, indicating that this animal model will be very useful for testing immunomodulatory anti-IL-10 and other therapies.

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Leishmania Chagasi Antigens Recognized in Cured Visceral Leishmaniasis and Asymptomatic Infection

Cited by 31 publications

References 0 publications

Elongation Factor-2, a Th1 Stimulatory Protein of Leishmania donovani, Generates Strong IFN-γ and IL-12 Response in Cured Leishmania-Infected Patients/Hamsters and Protects Hamsters against Leishmania Challenge

Elongation Factor-2, a Th1 Stimulatory Protein of Leishmania donovani, Generates Strong IFN-γ and IL-12 Response in Cured Leishmania-Infected Patients/Hamsters and Protects Hamsters against Leishmania Challenge

Th1 Cell-Mediated Resistance to Cutaneous Infection with Leishmania major Is Independent of P- and E-Selectins

Immunologic Indicators of Clinical Progression during CanineLeishmania infantumInfection

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