title: Nocardia brasiliensis induces an immunosuppressive microenvironment that favors chronic infection in BALB/c mice.
abstract: Nocardia brasiliensis is an intracellular microorganism and the most common etiologic agent of actinomycetoma in the Americas. Several intracellular pathogens induce an immunosuppressive microenvironment through increases in CD4+ Foxp3+ regulatory T cells (Treg), thus downregulating other T-cell subpopulations and assuring survival in the host. In this study, we determined whether N. brasiliensis modulates T-lymphocyte responses and their related cytokine profiles in a murine experimental model. We also examined the relationship between N. brasiliensis immunomodulation and pathogenesis and bacterial survival. In early infection, Th17/Tc17 cells were increased at day 3 (P < 0.05) in footpad tissue and spleen. Treg subpopulations peaked at days 7 and 15 (P < 0.01) in the footpad and spleen, respectively. Transforming growth factor β1 (TGF-β1) and interleuki-10 (IL-10) are cytokines known for their immunosuppressive effects. During early and chronic infections, these cytokines were elevated with increased TGF-β1 levels from days 3 to 30 (P < 0.01) and sustained IL-10 expression throughout infection compared to uninfected mice. IL-6 production was increased at day 3 (P < 0.01), whereas gamma interferon (IFN-γ), IL-17A, and IL-23 levels were highest at day 15 postinfection (P < 0.01) when a decrease in the bacterial load (>1 log) was also observed (P < 0.05). After these changes, at 30 to 60 days postinfection, IFN-γ production was decreased, whereas the expression of anti-inflammatory cytokines and the bacterial load again increased (P < 0.05). The increment in Treg cells and the related cytokine profile correlated with reduced inflammation at day 15 (P < 0.05) in the footpad. We conclude that N. brasiliensis modulates the immune system to induce an immunosuppressive microenvironment that benefits its survival during the chronic stage of infection.
authors.affiliation: Universidad Autonoma de Nuevo Leon, Department of Immunology, Faculty of Medicine, and University Hospital, Monterrey, Nuevo Leon, Mexico.
authors.forename: Adrian G
authors.initials: AG
authors.lastname: Rosas-Taraco
authors.forename: Amira R
authors.initials: AR
authors.lastname: Perez-Liñan
authors.forename: Paola
authors.initials: P
authors.lastname: Bocanegra-Ibarias
authors.forename: Luz I
authors.initials: LI
authors.lastname: Perez-Rivera
authors.forename: Mario C
authors.initials: MC
authors.lastname: Salinas-Carmona
mesh_terms: D000818:Animals; D058491:Bacterial Load; D002908:Chronic Disease; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D057131:Immune Evasion; D007108:Immune Tolerance; D051379:Mice; D008807:Mice, Inbred BALB C; D050296:Microbial Viability; D009615:Nocardia / Q000472:pathogenicity*; D009617:Nocardia Infections / Q000276:immunology* / Q000382:microbiology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology; D013997:Time Factors
chemical_list: D016207:Cytokines