TLR2-dependent mast cell activation contributes to the control of Mycobacterium tuberculosis infection.
Mast Cells (MCs) express toll-like receptor 2 (TLR2), a receptor known to be triggered by several major mycobacterial ligands and involved in resistance against Mycobacterium tuberculosis (MTB) infection. This study investigated whether adoptive transfer of TLR2 positive MCs (TLR2(+/+)) corrects the increased susceptibility of TLR2(-/-) mice to MTB infection. TLR2(-/-) mice displayed increased mycobacterial burden, diminished myeloid cell recruitment and proinflammatory cytokine production accompanied by defective granuloma formation. The reconstitution of these mice with TLR2(+/+) MCs, but not TLR2(-/-), confers better control of the infection, promotes the normalization of myeloid cell recruitment associated with reestablishment of the granuloma formation. In addition, adoptive transfer of TLR2(+/+) MC to TLR2(-/-) mice resulted in regulation of the pulmonary levels of IL-beta, IL-6, TNF-alpha, enhanced Th1 response and activated CD8(+) T cell homing to the lungs. Our results suggest that activation of MCs via TLR2 is required to compensate the defect in protective immunity and inability of TLR2(-/-) mice to control MTB infection.
Carlos
Daniela
D
Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, SP 14.040-903, Brazil.
Frantz
Fabiani G
FG
Souza-Júnior
Devandir A
DA
Jamur
Maria C
MC
Oliver
Constance
C
Ramos
Simone G
SG
Quesniaux
Valerie F
VF
Ryffel
Bernhard
B
Silva
Célio L
CL
Bozza
Marcelo T
MT
Faccioli
Lúcia H
LH
D019264:Adoptive Transfer; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002465:Cell Movement; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D006099:Granuloma / Q000276:immunology / Q000473:pathology; D008407:Mast Cells / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009169:Mycobacterium tuberculosis; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000378:metabolism*; D014397:Tuberculosis, Pulmonary / Q000276:immunology* / Q000517:prevention & control
D016207:Cytokines; C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2