title: C5aR contributes to the weak Th1 profile induced by an outbreak strain of Mycobacterium tuberculosis.
abstract: C5a anaphylatoxin is a component of the complement system involved in the modulation of T-cell polarization. Herein we investigated whether C5a receptors, C5aR and C5L2, modulate the cytokine profiles induced by Mycobacterium tuberculosis (Mtb). We analyzed the impact of both receptors on T helper cell polarization induced by the multidrug resistant outbreak strain named M, which is a poor IFN-γ inducer compared with the laboratory strain H37Rv. To this aim, we first blocked C5aR or C5L2 of peripheral blood monocytes (Mo) from patients with tuberculosis and healthy donors, then we stimulated the Mo either with H37Rv or the M strain, and finally we analyzed cytokine profiles of Mo/macrophages (MΦ) and CD4+T-cells. We found that: (i) Mtb modulated the expression of both C5a receptors, (ii) C5aR inhibited the expansion of CD4+IFN-γ+lymphocytes stimulated by the M strain but not by H37Rv, (iii) both receptors modulated the Mo/MΦ cytokine expression induced by Mtb. We conclude that C5aR, but not C5L2, plays a role in T helper cell polarization induced by Mtb and that this effect is strain- and donor-dependent. We speculate that the epidemiologically successful M strain takes advantage of this C5aR-mediated inhibition of Th1 polarization to survive within the host.
authors.affiliation: Instituto de Medicina Experimental (IMEX) - CONICET, Academia Nacional de Medicina, Ciudad Autónoma de Buenos Aires, Argentina. Electronic address: carmensabiogarcia@ege.fcen.uba.ar.
authors.forename: Carmen Alejandra
authors.initials: CA
authors.lastname: Sabio Y García
authors.affiliation: Instituto de Medicina Experimental (IMEX) - CONICET, Academia Nacional de Medicina, Ciudad Autónoma de Buenos Aires, Argentina.
authors.forename: Noemí
authors.initials: N
authors.lastname: Yokobori
authors.affiliation: Instituto de Medicina Experimental (IMEX) - CONICET, Academia Nacional de Medicina, Ciudad Autónoma de Buenos Aires, Argentina.
authors.forename: Juan Ignacio
authors.initials: JI
authors.lastname: Basile
authors.affiliation: Instituto de Medicina Experimental (IMEX) - CONICET, Academia Nacional de Medicina, Ciudad Autónoma de Buenos Aires, Argentina.
authors.forename: Luciana
authors.initials: L
authors.lastname: Balboa
authors.affiliation: Servicio de Neumonología, Hospital Nacional A. Posadas, Provincia de Buenos Aires, Argentina.
authors.forename: Alejandra
authors.initials: A
authors.lastname: González
authors.affiliation: Instituto Nacional de Enfermedades Infecciosas ANLIS "Carlos G. Malbrán", Ciudad Autónoma de Buenos Aires, Argentina.
authors.forename: Beatriz
authors.initials: B
authors.lastname: López
authors.affiliation: Instituto Nacional de Enfermedades Infecciosas ANLIS "Carlos G. Malbrán", Ciudad Autónoma de Buenos Aires, Argentina.
authors.forename: Viviana
authors.initials: V
authors.lastname: Ritacco
authors.affiliation: Instituto de Medicina Experimental (IMEX) - CONICET, Academia Nacional de Medicina, Ciudad Autónoma de Buenos Aires, Argentina.
authors.forename: Silvia de la
authors.initials: S
authors.lastname: Barrera
authors.affiliation: Instituto de Medicina Experimental (IMEX) - CONICET, Academia Nacional de Medicina, Ciudad Autónoma de Buenos Aires, Argentina.
authors.forename: María Del Carmen
authors.initials: MD
authors.lastname: Sasiain
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology* / Q000378:metabolism; D004196:Disease Outbreaks; D005260:Female; D005838:Genotype; D054884:Host-Pathogen Interactions; D006801:Humans; D008264:Macrophages / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D009169:Mycobacterium tuberculosis / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity; D010641:Phenotype; D044087:Receptor, Anaphylatoxin C5a / Q000276:immunology* / Q000378:metabolism; D019707:Receptors, Chemokine / Q000276:immunology / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D013997:Time Factors; D018088:Tuberculosis, Multidrug-Resistant / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D055815:Young Adult
chemical_list: C488033:C5AR1 protein, human; C417003:C5aR2 protein, human; D016207:Cytokines; D044087:Receptor, Anaphylatoxin C5a; D019707:Receptors, Chemokine
keywords: C5L2; C5aR; Complement C5a; Immune evasion; Th1-Th2 balance; Tuberculosis