Recognition of Mycobacterium tuberculosis by TLR2 and TLR9 in human alveolar macrophages and monocytes
Esmeralda Juárez Carvajal, Ma del Carmen Sarabia León, Dante Escobedo Sánchez, Eduardo Sada Díaz, Martha Torres Rojas
2010, Number 2
2010; 69 (2)
ABSTRACT
Background: Toll-like receptors (TLR) contribute to initial immune response to pathogens, however, their precise role in human alveolar macrophages response towards Mycobacterium tuberculosis (M. tuberculosis) remains poorly characterized. The aim of this study was to investigate this process in the alveolar and systemic compartments. Methods: TLR2 and TLR9 expression was determined in monocytes and alveolar macrophages stimulated with mycobacterial lipoarabinomannan and DNA or infected with the virulent strain of M. tuberculosis by flowcytometry. Ligand-specific and infection-induced production of proinflammatory cytokines was assessed by ELISA. Results: M. tuberculosis infection as well as stimulation with M. tuberculosis antigens modulated TLR2 but not TLR9 expression in monocytes and induced specific TNF-<6#945 and IL6 release. Alveolar macrophages did not modulated TLR2 nor TLR9 expression. Conclusions: Expression and function of TLR2 and TLR9 after exposure to M. tuberculosis is different between alveolar and systemic phagocytes. TLRs role in pulmonary defense may be relevant in the generation of immediate response as well as in control of M. tuberculosis infection.
Guth AM, Janssen WJ, Bosio CM, Crouch EC, HensonPM, Dow SW. Lung environment determines unique phenotype of alveolar macrophages. Am J Physiol Lung Cell Mol Physiol 2009;296:L936-L946.
Sibille Y, Reynolds HY. Macrophages and polymorphonuclear neutrophils in lung defense and injury. Am Rev Respir Dis 1990;141:471-501.
Taylor PR, Martinez-Pomares L, Stacey M, Lin HH, Brown GD, Gordon S. Macrophage receptors and immune recognition. Annu Rev Immunol 2005;23: 901-944.
Mukhopadhyay S, Herre J, Brown GD, Gordon S. The potential for Toll-like receptors to collaborate with other innate immune receptors. Immunology 2004;112:521- 530.
Roach JC, Glusman G, Rowen L, et ál. The evolution of vertebrate toll-like receptors. Proc Natl Acad Sci 2005;102:9577-9582.
Iwasaki A, Medzhitov R. Toll-like receptor control of theadaptive immune responses. Nat Immunol 2004;5:987-995.
Akira S, Takeda K, Kaisho T. Toll-like receptors: critical proteins linking innate and acquired immunity. Nat Immunol 2001;2:675-680.
Schluger NW, Rom WN. The host immune response to tuberculosis. Am J Respir Crit Care Med 1998;157:679- 691.
Underhill DM, Ozinsky A, Smith KD, Aderem A. Toll-like receptor-2 mediates mycobacteria-induced proinflammatory signaling in macrophages. Proc Natl Acad Sci USA 1999;96:14459-14463.
Uehori J, Matsumoto M, Tsuji S, et ál. Simultaneous blocking of human Toll-like receptors 2 and 4 suppresses myeloid dendritic cell activation induced by Mycobacterium bovis bacillus Calmette-Guérin peptidoglycan. Infect Immun 2003;71:4238-4249.
Means TK, Lien E, Yoshimura A, Wang S, Golenbock DT, Fenton MJ. The CD14 ligands lipoarabinomannan and lipopolysaccharide differ in their requirement for Tolllike receptors. J Immunol 1999;163:6748-6755.
Brightbill HD, Libraty DH, Krutzik SR, et ál. Host defense mechanisms triggered by microbial lipoproteinsthrough Toll-like receptors. Science 1999;285:732-736.
Ito T, Schaller M, Hogaboam CM, Standiford TJ, Chensue SW, Kunkel SL. TLR9 activation is a key event for the maintenance of a mycobacterial antigen-elicited pulmonary granulomatous response. Eur J Immunol 2007;37:2847- 2855.
Bafica A, Scanga CA, Feng CG, Leifer C, Cheever A,Sher A. TLR9 regulates Th1 responses and cooperates with TLR2 in mediating optimal resistance to Mycobacterium tuberculosis. J Exp Med 2005;202:1715- 1724.
Juárez E, Núñez C, Sada E, Ellner JJ, Schwander SK, Torres M. Differential expression of Toll-like receptors on human alveolar macrophages and autologous peripheral monocytes. Respir Res 2010;11:2.
Velez DR, Wejse C, Stryjewski ME, et ál. Variants in Tolllike receptors 2 and 9 influence susceptibility to pulmonary tuberculosis in Caucasians, African-Americans, and West Africans. Hum Genet 2010;127:65-73.
Hirsch CS, Ellner JJ, Russell DG, Rich EA. Complement receptor-mediated uptake and tumor necrosis factoralpha- mediated growth inhibition of Mycobacterium tuberculosis by human alveolar macrophages. J Immunol 1994;152:743-753.
Hopkins PA, Pridmore AC, Ellmerich S, et ál. Increased surface Toll-like receptor 2 expression in superantigen shock. Crit Care Med 2008;36:1267-1276.
Kincaid EZ, Wolf AJ, Desvignes L, et ál. Codominance of TLR2-dependent and TLR2-independent modulation of MHC class II in Mycobacterium tuberculosis infection in vivo. J Immunol 2007;179:3187-3195.
Raz E. Organ-specific regulation of innate immunity. Nat Immunol 2007;8:3-4.
Holt PG, Strickland DH, Wikström ME, Jahnsen FL. Regulation of immunological homeostasis in the respiratory tract. Nat Rev Immunol 2008;8: 142-152.
Ewald SE, Lee BL, Lau L, et ál. The ectodomain of Toll-like receptor 9 is cleaved to generate a functional receptor. Nature 2008;456:658-662.
Akira S, Takeda K, Kaisho T. Toll-like receptors: critical proteins linking innate and acquired immunity. Nat Immunol 2001;2:675-680.