2008, Number 39
Mycobacterium tuberculosis extracts induce the selective production of inflammatory cytokines and membrane receptors
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ABSTRACTBackground: In the early stages of tuberculosis, the levels of inflammatory cytokines increase, while Th1 and Th2 cytokines are produced later after T cells have been activated. CD14, CD64, CD206 and TLR4 receptors participate in the response against intracellular pathogens.
Objective: To analyze which fractions from Mycobacterium tuberculosis stimulate the expression of CD14, CD64, CD206, and TLR4, and their influence in the production of IL-1beta, IL-2, IL-4, IL-10, TNF-alpha and IFN-gamma.
Methods: Peripheral mononuclear cells from healthy PPD-positive volunteers were stimulated with M. tuberculosis: a) whole bacteria, b) secretory/excretory proteins from the bacteria, c) protein extract, d) lipidic extract, and e) polysaccharide extract. Cytokines from the supernatants were determined by ELISA, and surface molecules were analyzed by flow cytometry.
Results: Whole bacteria induced the expression of CD14, CD206, and the production of IFN-gamma, IL-1beta and IL-2. The protein extract induced the expression of CD14, CD206, and TLR4, and the production of IFN-gamma, TNF-alpha, IL-1beta and IL-2. The lipidic extract induced the expression of CD14, CD206, and the production of IFN-gamma. The polysaccharide extract induced the production of IL-10 and IFN-gamma. Secretory/excretory proteins induced the production of IFN-gamma and IL-2.
Conclusions: The protein and polysaccharides extracts of M. tuberculosis stimulate the production of important inflammatory cytokines and the expression of receptors in the membrane of mononuclear phagocytes to modulate the host’s immune system.
Takii T, Abe C, Tamura A, Ramayah S, et al. Interleukin-1 or tumor necrosis factor-alpha augmented the cytotoxic effect of mycobacteria on human fibroblasts: application to evaluation of pathogenesis of clinical isolates of Mycobacterium tuberculosis and M. avium complex. J Interferon Cytokine Res 2001;21:187-96.