Mem Inst Oswaldo Cruz, Rio de Janeiro, VOLUME 114 | JULY 2019
Original Article

The virulence variability associated with specific Mycobacterium tuberculosis clinical isolates alters the capacity of human dendritic cells to expand T cells [ACCEPTED ARTICLES / PRELIMINARY VERSION]

Ramos Martinez AG1, 2, Valtierra-Alvarado MA1, 2, Garcia-Hernandez MH1, Hernandez-Pando R3, Castañeda Delgado JE4, Cougoule C5, Rivas Santiago B1, Neyrolles O5, Enciso-Moreno J1, Lugo-Villarino G5, Serrano CJ1,+

1Unidad de Investigación Biomédica Zacatecas, Instituto Mexicano del Seguro Social, México
2Departamento de Inmunología, Escuela de Medicina, Universidad Autónoma de San Luis Potosí (UASLP), México
3Sección de Patología Experimental, Departamento de Patología, Instituto Nacional de Ciencias Médicas y de la Nutrición Salvador Zubirán, Ciudad de México,  México
4Cátedras CONACyT, Consejo Nacional de Ciencia y Tecnología (CONACyT- México), Unidad de Investigación Biomédica Zacatecas, Instituto Mexicano del Seguro Social. Zacatecas, México
5Institut de Pharmacologie et de Biologie Structurale, Université de Toulouse, CNRS, UPS, Toulouse, France

DOI: 10.1590/0074-02760190102
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ABSTRACT

The effect of the virulence of Mycobacterium tuberculosis (Mtb) during the interaction with human dendritic cells (DCs) has not been fully explored. Herein, we exposed human monocyte-derived DCs to Mtb clinical strains (isolated from an epidemiological diversity of Mtb strains study in Mexico) bearing different virulence degrees, and evaluated the capacity of DCs to internalize bacilli, control intracellular growth, engage cell death pathways, express markers for activation and antigen presentation, and expand autologous CD4+ T cells. In the case of the hypervirulent (Phenotype 1, strain 9005186, lineage 3) Mtb, we report that DCs internalize and neutralize its intracellular growth, undergo low rates of apoptosis, and poorly expand T cells, as compared to the H37Rv reference strain. In the case of the hypovirulent (Phenotype 4, strain 9985449, lineage 4) Mtb, while DCs internalize and preclude its proliferation, they displayed massive apoptosis levels that prevent them from maintaining autologous CD4+ T cells alive in a co-culture system, as compared to H37Rv. In general, our findings suggest that virulence variance among these Mtb clinical strains impacts the capacity of DCs to respond to pathogenic challenge and mount an immune response against it, highlighting important parallels from studies done in the mouse model.

This work was supported by Fondo de Investigación en Salud from Instituto Mexicano del Seguro Social, México (grant number FIS/IMSS/PROT/MD15/1489) and, Agence Nationale de la Recherche, France (grant number ANR-15-CE15-0012, MMI-TB). AGRM and MAVA were supported by Consejo Nacional de Ciencia y Tecnología, México (CONACyT) during their PhD studies (fellowship Numbers 417995 and 584982).
VAMA and RMAG contributed equally.
LVG and SCJ are co-senior authors.
+ Corresponding-author: carmenyuyu2000@yahoo.com.mx
https://orcid.org/0000-0002-7047-9120
Received 22 March 2019
Accepted 08 July 2019

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