Variability in the virulence of specific Mycobacterium tuberculosis clinical isolates alters the capacity of human dendritic cells to signal for T cells

Autor: Cappoen, Davie, Torfs, Eveline, Meiresonne, Tamara, Claes, Pieter, Semina, Elena, Holvoet, Francis, de Macedo, Maíra Bidart, Cools, Freya, Piller, Tatiana, Matheeussen, An, Van Calster, Kevin, Caljon, Guy, Delputte, Peter, Maes, Louis, De Kimpe, Norbert, Mangelinckx, Sven, Cos, Paul, Ramos-Martinez, Ana Gabriela, Valtierra-Alvarado, Monica Alejandra, Garcia-Hernandez, Mariana Haydee, Hernandez-Pando, Rogelio, Castañeda-Delgado, Julio Enrique, Cougoule, Céline, Rivas-Santiago, Bruno, Neyrolles, Olivier, Enciso-Moreno, Jose Antonio, Lugo-Villarino, Geanncarlo, Serrano, Carmen Judith
Přispěvatelé: Department of Pathology, INCMNSZ, INNSZ, Institut de pharmacologie et de biologie structurale (IPBS), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), University of Antwerp (UA), Laboratory of Microbiology, Parasitology and Hygiene [Antwerpen] (LMPH)
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Zdroj: Memórias do Instituto Oswaldo Cruz
Memórias do Instituto Oswaldo Cruz, Instituto Oswaldo Cruz, Ministério da Saúde, 2019, 114, ⟨10.1590/0074-02760190102⟩
Memórias do Instituto Oswaldo Cruz., Vol 114
Memórias do Instituto Oswaldo Cruz.
Memórias do Instituto Oswaldo Cruz., Instituto Oswaldo Cruz, Ministério da Saúde, 2019, 114, ⟨10.1590/0074-02760190102⟩
Memórias do Instituto Oswaldo Cruz., Instituto Oswaldo Cruz, Ministério da Saúde, 2019, 114, pp.111549. ⟨10.1590/0074-02760190102⟩
Memórias do Instituto Oswaldo Cruz, Volume: 114, Article number: e190102, Published: 12 AUG 2019
ISSN: 0074-0276
1678-8060
Popis: International audience; BACKGROUND Once in the pulmonary alveoli, Mycobacterium tuberculosis (Mtb) enters into contact with alveolar macrophages and dendritic cells (DCs). DCs represent the link between the innate and adaptive immune system owing to their capacity to be both a sentinel and an orchestrator of the antigen-specific immune responses against Mtb. The effect that the virulence of Mtb has on the interaction between the bacilli and human DCs has not been fully explored.OBJECTIVE To evaluate the effect of Mtb virulence on human monocyte-derived DCs.METHODS We exposed human monocyte-derived DCs to Mtb clinical strains (isolated from an epidemiological Mtb diversity study in Mexico) bearing different degrees of virulence and evaluated the capacity of DCs to internalise the bacilli, control intracellular growth, engage cell death pathways, express markers for activation and antigen presentation, and expand to stimulate autologous CD4+ T cells proliferation.FINDINGS In the case of the hypervirulent Mtb strain (Phenotype 1, strain 9005186, lineage 3), we report that DCs internalise and neutralise intracellular growth of the bacilli, undergo low rates of apoptosis, and contribute poorly to T-cell expansion, as compared to the H37Rv reference strain. In the case of the hypovirulent Mtb strain (Phenotype 4, strain 9985449, lineage 4), although DCs internalise and preclude proliferation of the bacilli, the DCs also display a high level of apoptosis, massive levels of apoptosis that prevent them from maintaining autologous CD4+ T cells in a co-culture system, as compared to H37Rv. MAIN CONCLUSIONS Our findings suggest that variability in virulence among Mtb clinical strains affects the capacity of DCs to respond to pathogenic challenge and mount an immune response against it, highlighting important parallels to studies previously done in mouse models.
Databáze: OpenAIRE
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