In Situ versus Systemic Immune Response in the Pathogenesis of Cutaneous Leishmaniasis

Author:

Carvalho Augusto M.123,Costa Rúbia S.12,Lago Alexsandro2,Bacellar Olívia23ORCID,Beiting Daniel P.4,Scott Phillip4,Carvalho Lucas P.123ORCID,Carvalho Edgar M.123ORCID

Affiliation:

1. Gonçalo Moniz Institute (IGM), Fiocruz, Salvador 40296-710, BA, Brazil

2. Immunology Service, Professor Edgard Santos University Hospital Complex, Federal University of Bahia, Salvador 40110-160, BA, Brazil

3. Instituto Nacional de Ciência e Tecnologia em Doenças Tropicais (INCT-DT), Ministério da Ciência e Tecnologia e Inovação (MCTI), CNPq, Salvador 40110-160, BA, Brazil

4. Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104-4539, USA

Abstract

The role of the immune response in the pathogenesis of cutaneous leishmaniasis (CL) due to Leishmania (Viannia) braziliensis is predominantly carried out via blood cells. Here, we evaluate whether cytokine production by peripheral blood mononuclear cells (PBMCs) reflects what has been documented at the lesion site. The participants included 22 CL patients diagnosed with a positive PCR. PBMCs were stimulated for 72 h with a soluble leishmania antigen (SLA). Biopsies obtained from the edge of the ulcers were incubated for the same period. Cytokines in supernatants were assessed via ELISA. TNF, IL-1β, IL-6, IL-17, and granzyme B (GzmB) were higher in the supernatants of biopsies than in PBMCs, but IFN-γ was higher in the supernatants of PBMCs than in biopsies. There was a positive correlation between IFN-γ and TNF in PBMCs, and an inverse correlation between TNF and IL-10 in the cells from the lesion site. A strong correlation between IL-1β, IL-17, and GzmB was observed in the biopsies, and a positive correlation was detected between these cytokines and the lesion size. Our results indicate that the immune response in L. braziliensis lesions is different from that observed in peripheral blood, and our data suggest that in addition to IL-1β and GzmB, IL-17 participates in the pathology of CL.

Funder

Brazilian Ministry of Science, Technology, and Innovation

Fundação de Amparo à Pesquisa do Estado da Bahia

National Institutes of Health

Publisher

MDPI AG

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