title: Immunoregulatory and Effector Activities in Human Cutaneous and Mucosal Leishmaniasis: Understanding Mechanisms of Pathology.
abstract: Individuals infected withLeishmania braziliensismay develop the relatively benign localized cutaneous (CL) form or the mucosal (ML) form of the disease, which represents a more severe and mutilating variation. Interaction between parasite and host cells, as well as the genetic background of the host, are important determinants of the immune response, which is critical in determining disease outcome. Our studies over the years have been designed to determine the immunoregulatory and effector functions that culminate in the formation of lesions in CL and ML disease and how these host response factors may be better understood for design of novel therapies and prophylaxis. By studying the immune response from CL and ML patients in both the peripheral blood and in situ, we have learned much concerning the dynamics of the host-pathogen interaction that leads to the development of CL and ML. We used multiparameter flow cytometry to study the immunoregulatory profiles of the peripheral blood leukocytes, as well as laser scanning confocal microscopy to examine in situ several aspects of the local response, including the intensity of the inflammatory infiltrate, the cellular composition, inflammatory and anti-inflammatory cytokine expression, and the expression of the effector cytotoxic molecule, granzyme A, in lesions from CL and ML patients. Moreover, the application of correlative analysis between these immunological parameters has helped shed light on disease progression in CL and ML. These findings are reviewed within the context of understanding cellular and molecular mechanisms associated with the development of pathology in these diseases through a comparative analysis of the clinical forms, CL and ML, as well as of studies derived from peripheral blood and lesions.
authors.affiliation: Departamento de Morfologia, Laboratório de Biologia das Interações Celulares, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG 31270, Brazil ; Tropical Disease Research Program, Center for Infectious Disease Research, Biosciences Division, SRI International, Menlo Park, CA 94025 ; Instituto Nacional de Ciência e Tecnologia, Doenças Tropicais, Belo Horizonte, MG 31270, Brazil.
authors.forename: Walderez O
authors.initials: WO
authors.lastname: Dutra
authors.forename: Daniela Rodrigues
authors.initials: DR
authors.lastname: de Faria
authors.forename: Paulo Roberto
authors.initials: PR
authors.lastname: Lima Machado
authors.forename: Luiz Henrique
authors.initials: LH
authors.lastname: Guimarães
authors.forename: Albert
authors.initials: A
authors.lastname: Schriefer
authors.forename: Edgar
authors.initials: E
authors.lastname: Carvalho
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: Gollob
keywords: human; immunoregulation; leishmaniasis; pathology