Cytotoxic T Cells Mediate Pathology and Metastasis in Cutaneous Leishmaniasis
نویسندگان
چکیده
Disease progression in response to infection can be strongly influenced by both pathogen burden and infection-induced immunopathology. While current therapeutics focus on augmenting protective immune responses, identifying therapeutics that reduce infection-induced immunopathology are clearly warranted. Despite the apparent protective role for murine CD8⁺ T cells following infection with the intracellular parasite Leishmania, CD8⁺ T cells have been paradoxically linked to immunopathological responses in human cutaneous leishmaniasis. Transcriptome analysis of lesions from Leishmania braziliensis patients revealed that genes associated with the cytolytic pathway are highly expressed and CD8⁺ T cells from lesions exhibited a cytolytic phenotype. To determine if CD8⁺ T cells play a causal role in disease, we turned to a murine model. These studies revealed that disease progression and metastasis in L. braziliensis infected mice was independent of parasite burden and was instead directly associated with the presence of CD8⁺ T cells. In mice with severe pathology, we visualized CD8⁺ T cell degranulation and lysis of L. braziliensis infected cells. Finally, in contrast to wild-type CD8⁺ T cells, perforin-deficient cells failed to induce disease. Thus, we show for the first time that cytolytic CD8⁺ T cells mediate immunopathology and drive the development of metastatic lesions in cutaneous leishmaniasis.
منابع مشابه
The Histopathological Changes and Immunohistochemical Findings of Acute, Chronic Nonlupoid and Chronic Lupoid Types of Cutaneous Leishmaniasis
Background & Aims: Dry type localized cutaneous Leishmaniasis due to Leishmania tropica is one of the most prevalent cutaneous parasitic infections in Kerman province. It seems that cellular immune response and the nature of immune inflammatory cells comprising the inflammatory background play a determinant role in this infection. Methods: Skin biopsies of 53 patients with acute(<2 years durati...
متن کاملPossible Interrelationship of Inflammatory Cells in Dry Type Cutaneous leishmaniasis
Background & Objective: There is a complicated interaction between leishmaniasis and the host immune cells, and also between the host immune cells. These interactions have fundamental effects on the outcome of the disease. The current study aimed at characterizing the number, distribution, co-localization, and interrelation of 4 types of inflamma...
متن کاملLocalized Leishmania Lymphadenitis: A Morphologic and Immunohistochemical Study
Localized Leishmania Lymphadenitis (L.L.L) is a self limited clinical presentation of cutaneous leishmaniasis. Microscopic findings in L.L.L are very similar to Toxoplasma lymphasenitis. In all cases, an intensive microscopic search should be done for Leishman bodies. In this study, we describe our micro...
متن کاملA Rare Case of Cutaneous Leishmaniasis Presenting as Rhinophyma
Cutaneous leishmaniasis(CL) is referred to a group of diseases because of the varied clinical presentation, ranging from small cutaneous nodule to wide spread mucosal destruction. The nose is rarely involved by CL in even in endemic region. In this report we describe a rare rhinophymatous presentation of CL from a non-endemic region which was diagnosed by fine needle sampling and treated with M...
متن کاملCytotoxic activity in cutaneous leishmaniasis
Cutaneous leishmaniasis (CL) is a chronic disease caused by species of the protozoan Leishmania and characterised by the presence of ulcerated skin lesions. Both parasite and host factors affect the clinical presentation of the disease. The development of skin ulcers in CL is associated with an inflammatory response mediated by cells that control parasite growth but also contribute to pathogene...
متن کامل