title: Protein malnutrition promotes dysregulation of molecules involved in T cell migration in the thymus of mice infected with Leishmania infantum.
abstract: Protein malnutrition, the most deleterious cause of malnutrition in developing countries, has been considered a primary risk factor for the development of clinical visceral leishmaniasis (VL). Protein malnutrition and infection with Leishmania infantum leads to lymphoid tissue disorganization, including changes in cellularity and lymphocyte subpopulations in the thymus and spleen. Here we report that protein malnutrition modifies thymic chemotactic factors by diminishing the CCL5, CXCL12, IGF1, CXCL9 and CXCL10 protein levels in infected animals. Nevertheless, T cells preserve their migratory capability, as they were able to migrate ex vivo in response to chemotactic stimuli, indicating that malnutrition may compromise the thymic microenvironment and alter in vivo thymocyte migration. Decrease in chemotactic factors protein levels was accompanied by an early increase in the parasite load of the spleen. These results suggest that the precondition of malnutrition is affecting the cell-mediated immune response to L. infantum by altering T cell migration and interfering with the capacity of protein-deprived animals to control parasite spreading and proliferation. Our data provide evidence for a disturbance of T lymphocyte migration involving both central and peripheral T-cells, which likely contribute to the pathophysiology of VL that occurs in malnourished individuals.
authors.affiliation: Laboratório de Pesquisas em Leishmaniose, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro, RJ, Brasil.
authors.forename: Monica
authors.initials: M
authors.lastname: Losada-Barragán
authors.affiliation: Departamento de Química, Universidad Nacional de Colombia, Sede Bogotá, Facultad de Ciencias, Grupo de Investigación en Hormonas, Bogotá, Colombia.
authors.forename: Adriana
authors.initials: A
authors.lastname: Umaña-Pérez
authors.affiliation: Departamento de Química, Universidad Nacional de Colombia, Sede Bogotá, Facultad de Ciencias, Grupo de Investigación en Hormonas, Bogotá, Colombia.
authors.forename: Sergio
authors.initials: S
authors.lastname: Cuervo-Escobar
authors.affiliation: Laboratório de Pesquisas sobre o Timo, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro, RJ, Brasil.
authors.forename: Luiz Ricardo
authors.initials: LR
authors.lastname: Berbert
authors.affiliation: Laboratório de Pesquisas em Leishmaniose, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro, RJ, Brasil.
authors.forename: Renato
authors.initials: R
authors.lastname: Porrozzi
authors.affiliation: Laboratório de Pesquisas em Leishmaniose, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro, RJ, Brasil.
authors.forename: Fernanda N
authors.initials: FN
authors.lastname: Morgado
authors.affiliation: Laboratório de Pesquisas sobre o Timo, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro, RJ, Brasil.
authors.forename: Daniella Areas
authors.initials: DA
authors.lastname: Mendes-da-Cruz
authors.affiliation: Laboratório de Pesquisas sobre o Timo, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro, RJ, Brasil.
authors.forename: Wilson
authors.initials: W
authors.lastname: Savino
authors.affiliation: Departamento de Química, Universidad Nacional de Colombia, Sede Bogotá, Facultad de Ciencias, Grupo de Investigación en Hormonas, Bogotá, Colombia. mysanchezd@unal.edu.co.
authors.forename: Myriam
authors.initials: M
authors.lastname: Sánchez-Gómez
authors.affiliation: Laboratório de Pesquisas em Leishmaniose, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro, RJ, Brasil. patricia.cuervo@fiocruz.br.
authors.forename: Patricia
authors.initials: P
authors.lastname: Cuervo
mesh_terms: D000818:Animals; D017209:Apoptosis; D001284:Atrophy; D001835:Body Weight; D002465:Cell Movement; D002633:Chemotaxis; D016207:Cytokines / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D018314:Leishmania infantum / Q000472:pathogenicity*; D007898:Leishmaniasis, Visceral / Q000097:blood / Q000150:complications* / Q000276:immunology* / Q000469:parasitology; D020738:Leptin / Q000097:blood; D008024:Ligands; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D044342:Malnutrition / Q000097:blood / Q000150:complications* / Q000276:immunology* / Q000469:parasitology; D008807:Mice, Inbred BALB C; D059208:Parasite Load; D010271:Parasites / Q000472:pathogenicity; D054367:Receptors, CXCR3 / Q000378:metabolism; D013154:Spleen / Q000469:parasitology; D013601:T-Lymphocytes / Q000473:pathology*; D060168:Thymocytes / Q000473:pathology; D013950:Thymus Gland / Q000473:pathology*
chemical_list: D016207:Cytokines; D020738:Leptin; D008024:Ligands; D054367:Receptors, CXCR3; D007334:Insulin-Like Growth Factor I