title: Mycobacterium tuberculosis may escape helper T cell recognition by infecting human fibroblasts.
abstract: The host immune response can limit Mycobacterium tuberculosis (Mtb) spreading in primary tuberculosis (TB) without eradicating all bacilli, which can persist causing latent TB infection and are responsible for reactivation TB. Persistent Mtb is confined to granulomas within phagocytes, but it is also found in other non-immune cells. We focused on fibroblasts since these cells participate to the granuloma formation and were shown to be infected in latent TB infections. We show that in vitro both Mtb and Bacille Calmette-Guérin actively replicate in human fibroblasts. Mycobacterial infection of fibroblasts causes a significant inhibition of interferon (IFN)-γ induced membrane expression of major histocompatibility complex class II molecules in these cells. The functional consequence of in vitro infection is a significant reduction of the fibroblast capacity to present peptides and soluble proteins to autologous specific CD4(+) T cell clones. Moreover, fibroblasts are capable of presenting antigen derived from the processing of heat-killed Mtb, but not from viable Mtb. Data indicate that IFN-γ treated fibroblasts are capable of presenting antigens derived from the processing of whole bacteria in addition to the capacity to present peptides and isolated proteins. Interestingly, Mtb infected fibroblasts lose this capacity, suggesting that Mtb may evade T helper immune surveillance by infecting fibroblasts.
authors: Dipartimento di Malattie Infettive, Parassitarie e Immunomediate, Istituto Superiore di Sanità, Roma, Italy.
authors: Sabrina
authors: S
authors: Mariotti
authors: Valeria
authors: V
authors: Sargentini
authors: Manuela
authors: M
authors: Pardini
authors: Federico
authors: F
authors: Giannoni
authors: Marco
authors: M
authors: De Spirito
authors: Maria Cristina
authors: MC
authors: Gagliardi
authors: Emanuela
authors: E
authors: Greco
authors: Raffaela
authors: R
authors: Teloni
authors: Maurizio
authors: M
authors: Fraziano
authors: Roberto
authors: R
authors: Nisini
mesh_terms: D017951:Antigen Presentation / Q000276:immunology; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D049109:Cell Proliferation; D005347:Fibroblasts / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D009169:Mycobacterium tuberculosis / Q000276:immunology* / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000378:metabolism
chemical_list: D000949:Histocompatibility Antigens Class II; D007371:Interferon-gamma