TY - JOUR
T1 - Mycobacterium tuberculosis Cell Wall Antigens Induce the Formation of Immune Complexes and the Development of Vasculitis in an Experimental Murine Model
AU - Pérez-Noriega, Flaubert Alexis
AU - Salinas-Lara, Citlaltepetl
AU - Sánchez-Garibay, Carlos
AU - Torres-Ruíz, José Jiram
AU - Maravillas-Montero, José Luis
AU - Castañón-Arreola, Mauricio
AU - Hernández-Campos, María Elena
AU - Rodríguez-Balderas, Cesar
AU - Basurto-López, Beatriz Victoria
AU - Peñafiel-Salgado, Carlos
AU - Espinosa-García, Ana Paola
AU - Choreño-Parra, José Alberto
AU - Tena-Suck, Martha Lilia
AU - Soto-Rojas, Luis O.
AU - León-Marroquín, Elsa Y.
AU - Romero-López, José Pablo
AU - Castillejos-López, Manuel
N1 - Publisher Copyright:
© 2023 by the authors.
PY - 2023/1
Y1 - 2023/1
N2 - Tuberculosis (TB) of the central nervous system (CNS) presents high mortality due to brain damage and inflammation events. The formation and deposition of immune complexes (ICs) in the brain microvasculature during Mycobacterium tuberculosis (Mtb) infection are crucial for its pathobiology. The relevance of ICs to Mtb antigens in the pathogenesis of CNS-TB has been poorly explored. Here, we aimed to establish a murine experimental model of ICs-mediated brain vasculitis induced by cell wall antigens of Mtb. We administered a cell wall extract of the prototype pathogenic Mtb strain H37Rv to male BALB/c mice by subcutaneous and intravenous routes. Serum concentration and deposition of ICs onto blood vessels were determined by polyethylene glycol precipitation, ELISA, and immunofluorescence. Histopathological changes in the brain, lung, spleen, liver, and kidney were evaluated by hematoxylin and eosin staining. Our results evidenced that vasculitis developed in the studied tissues. High serum levels of ICs and vascular deposition were evident in the brain, lung, and kidneys early after the last cell wall antigen administration. Cell wall Mtb antigens induce strong type III hypersensitivity reactions and the development of systemic vasculitis with brain vascular changes and meningitis, supporting a role for ICs in the pathogenesis of TB.
AB - Tuberculosis (TB) of the central nervous system (CNS) presents high mortality due to brain damage and inflammation events. The formation and deposition of immune complexes (ICs) in the brain microvasculature during Mycobacterium tuberculosis (Mtb) infection are crucial for its pathobiology. The relevance of ICs to Mtb antigens in the pathogenesis of CNS-TB has been poorly explored. Here, we aimed to establish a murine experimental model of ICs-mediated brain vasculitis induced by cell wall antigens of Mtb. We administered a cell wall extract of the prototype pathogenic Mtb strain H37Rv to male BALB/c mice by subcutaneous and intravenous routes. Serum concentration and deposition of ICs onto blood vessels were determined by polyethylene glycol precipitation, ELISA, and immunofluorescence. Histopathological changes in the brain, lung, spleen, liver, and kidney were evaluated by hematoxylin and eosin staining. Our results evidenced that vasculitis developed in the studied tissues. High serum levels of ICs and vascular deposition were evident in the brain, lung, and kidneys early after the last cell wall antigen administration. Cell wall Mtb antigens induce strong type III hypersensitivity reactions and the development of systemic vasculitis with brain vascular changes and meningitis, supporting a role for ICs in the pathogenesis of TB.
KW - M. tuberculosis
KW - antigens
KW - cell wall
KW - immunecomplexes
KW - murine model
KW - type III hypersensitivity
KW - vasculitis
UR - http://www.scopus.com/inward/record.url?scp=85146773155&partnerID=8YFLogxK
U2 - 10.3390/ijms24021242
DO - 10.3390/ijms24021242
M3 - Artículo
C2 - 36674759
AN - SCOPUS:85146773155
SN - 1661-6596
VL - 24
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
IS - 2
M1 - 1242
ER -