Inhibition of Toll-like Receptor 2 (TLR-2)-mediated Response in Human Alveolar Epithelial Cells by Mycolic Acids and Mycobacterium Tuberculosis Mce1 Operon Mutant

Overview

Journal Pathog Dis

Publisher Oxford University Press

Specialties Infectious Diseases
Microbiology

Date 2013 Nov 6

PMID 24190334

Citations 21

Authors

Patricia C Sequeira

Ryan H Senaratne

Lee W Riley

Affiliations

Soon will be listed here.

Abstract

In human lungs, the earliest encounter of Mycobacterium tuberculosis, the agent of tuberculosis, involves alveolar epithelial cells. Droplets expectorated by a patient with tuberculosis are likely to contain a mixed population of M. tuberculosis cells in different physiologic and metabolic states from the lung lesions of the patient. Here, we compared the chemokine expression patterns of human epithelial cell line A549 and RAW 264.7 macrophage cells infected with wild-type M. tuberculosis H37Rv against patterns induced by a mutant that accumulates free mycolic acids in its cell wall (Δmce1). We also examined the effect of free mycolic acids on toll-like receptor-2 (TLR-2). Wild-type M. tuberculosis induced significantly higher levels of IL-8, MCP-1, RANTES, and IP-10 in both cell types than did Δmce. Free mycolic acids reduced the ability of the mammalian cells to respond to a TLR-2 agonist in a dose-dependent manner. These observations suggest that differences in mycolic acid abundance in the M. tuberculosis cell wall can affect TLR-2-mediated pro-inflammatory response in both epithelial and macrophage cells. The final fate of a new infection may be ultimately determined by the proportion of M. tuberculosis cells expressing free mycolates in the infecting inoculum population.

Citing Articles

The CRISPR-dCas9 interference system suppresses inhA gene expression in Mycobacterium smegmatis.

Singpanomchai N, Ratthawongjirakul P Sci Rep. 2024; 14(1):26116.

PMID: 39478003 PMC: 11525817. DOI: 10.1038/s41598-024-77442-2.

Significance of genotypes and resistance status of strains in gene expression of apoptosis cell death and inflammatory pathways in A549 lung epithelial cell line.

Abdolhamidi R, Haghighat S, Moshiri A, Fateh A, Siadat S Iran J Basic Med Sci. 2024; 27(7):825-831.

PMID: 38800030 PMC: 11127082. DOI: 10.22038/IJBMS.2024.75195.16303.

and infect epithelial cells via different strategies.

Hu R, Wan L, Liu X, Lu J, Hu X, Zhang X J Thorac Dis. 2023; 15(8):4396-4412.

PMID: 37691650 PMC: 10482649. DOI: 10.21037/jtd-23-493.

Mycobacterium tuberculosis and its clever approaches to escape the deadly macrophage.

Krishnan V, Nath S, Nair P, Das B World J Microbiol Biotechnol. 2023; 39(11):300.

PMID: 37667129 DOI: 10.1007/s11274-023-03735-9.

Pathogenicity and virulence of .

Rahlwes K, Dias B, Campos P, Alvarez-Arguedas S, Shiloh M Virulence. 2022; 14(1):2150449.

PMID: 36419223 PMC: 9817126. DOI: 10.1080/21505594.2022.2150449.

References

de la Paz Santangelo M, Klepp L, Nunez-Garcia J, Blanco F, Soria M, Garcia-Pelayo M . Mce3R, a TetR-type transcriptional repressor, controls the expression of a regulon involved in lipid metabolism in Mycobacterium tuberculosis. Microbiology (Reading). 2009; 155(Pt 7):2245-2255. DOI: 10.1099/mic.0.027086-0. View

Sano H, Kuroki Y . The lung collectins, SP-A and SP-D, modulate pulmonary innate immunity. Mol Immunol. 2004; 42(3):279-87. DOI: 10.1016/j.molimm.2004.07.014. View

Harding C, Boom W . Regulation of antigen presentation by Mycobacterium tuberculosis: a role for Toll-like receptors. Nat Rev Microbiol. 2010; 8(4):296-307. PMC: 3037727. DOI: 10.1038/nrmicro2321. View

Ehlers S . DC-SIGN and mannosylated surface structures of Mycobacterium tuberculosis: a deceptive liaison. Eur J Cell Biol. 2009; 89(1):95-101. DOI: 10.1016/j.ejcb.2009.10.004. View

Birchler T, Seibl R, Buchner K, Loeliger S, Seger R, Hossle J . Human Toll-like receptor 2 mediates induction of the antimicrobial peptide human beta-defensin 2 in response to bacterial lipoprotein. Eur J Immunol. 2001; 31(11):3131-7. DOI: 10.1002/1521-4141(200111)31:11<3131::aid-immu3131>3.0.co;2-g. View

Fulton S, Reba S, Pai R, Pennini M, Torres M, Harding C . Inhibition of major histocompatibility complex II expression and antigen processing in murine alveolar macrophages by Mycobacterium bovis BCG and the 19-kilodalton mycobacterial lipoprotein. Infect Immun. 2004; 72(4):2101-10. PMC: 375182. DOI: 10.1128/IAI.72.4.2101-2110.2004. View

Dunphy K, Senaratne R, Masuzawa M, Kendall L, Riley L . Attenuation of Mycobacterium tuberculosis functionally disrupted in a fatty acyl-coenzyme A synthetase gene fadD5. J Infect Dis. 2010; 201(8):1232-9. PMC: 3225055. DOI: 10.1086/651452. View

Lima P, Sidders B, Morici L, Reader R, Senaratne R, Casali N . Enhanced mortality despite control of lung infection in mice aerogenically infected with a Mycobacterium tuberculosis mce1 operon mutant. Microbes Infect. 2007; 9(11):1285-90. PMC: 2894154. DOI: 10.1016/j.micinf.2007.05.020. View

Ferguson J, Voelker D, McCormack F, Schlesinger L . Surfactant protein D binds to Mycobacterium tuberculosis bacilli and lipoarabinomannan via carbohydrate-lectin interactions resulting in reduced phagocytosis of the bacteria by macrophages. J Immunol. 1999; 163(1):312-21. View

10.

Rivas-Santiago B, Hernandez-Pando R, Carranza C, Juarez E, Contreras J, Aguilar-Leon D . Expression of cathelicidin LL-37 during Mycobacterium tuberculosis infection in human alveolar macrophages, monocytes, neutrophils, and epithelial cells. Infect Immun. 2007; 76(3):935-41. PMC: 2258801. DOI: 10.1128/IAI.01218-07. View

11.

Casali N, Riley L . A phylogenomic analysis of the Actinomycetales mce operons. BMC Genomics. 2007; 8:60. PMC: 1810536. DOI: 10.1186/1471-2164-8-60. View

12.

Scanga C, Bafica A, Feng C, Cheever A, Hieny S, Sher A . MyD88-deficient mice display a profound loss in resistance to Mycobacterium tuberculosis associated with partially impaired Th1 cytokine and nitric oxide synthase 2 expression. Infect Immun. 2004; 72(4):2400-4. PMC: 375220. DOI: 10.1128/IAI.72.4.2400-2404.2004. View

13.

Segal W, Bloch H . Pathogenic and immunogenic differentiation of Mycobacterium tuberculosis grown in vitro and in vivo. Am Rev Tuberc. 1957; 75(3):495-500. DOI: 10.1164/artpd.1957.75.3.495. View

14.

Casali N, White A, Riley L . Regulation of the Mycobacterium tuberculosis mce1 operon. J Bacteriol. 2005; 188(2):441-9. PMC: 1347267. DOI: 10.1128/JB.188.2.441-449.2006. View

15.

Herrmann J, Lagrange P . Dendritic cells and Mycobacterium tuberculosis: which is the Trojan horse?. Pathol Biol (Paris). 2004; 53(1):35-40. DOI: 10.1016/j.patbio.2004.01.004. View

16.

Kohwiwattanagun J, Kawamura I, Fujimura T, Mitsuyama M . Mycobacterial mammalian cell entry protein 1A (Mce1A)-mediated adherence enhances the chemokine production by A549 alveolar epithelial cells. Microbiol Immunol. 2007; 51(2):253-61. DOI: 10.1111/j.1348-0421.2007.tb03897.x. View

17.

Shimono N, Morici L, Casali N, Cantrell S, Sidders B, Ehrt S . Hypervirulent mutant of Mycobacterium tuberculosis resulting from disruption of the mce1 operon. Proc Natl Acad Sci U S A. 2003; 100(26):15918-23. PMC: 307668. DOI: 10.1073/pnas.2433882100. View

18.

Asai Y, Jinno T, Ogawa T . Oral treponemes and their outer membrane extracts activate human gingival epithelial cells through toll-like receptor 2. Infect Immun. 2003; 71(2):717-25. PMC: 145376. DOI: 10.1128/IAI.71.2.717-725.2003. View

19.

Hall-Stoodley L, Watts G, Crowther J, Balagopal A, Torrelles J, Robison-Cox J . Mycobacterium tuberculosis binding to human surfactant proteins A and D, fibronectin, and small airway epithelial cells under shear conditions. Infect Immun. 2006; 74(6):3587-96. PMC: 1479241. DOI: 10.1128/IAI.01644-05. View

20.

Armstrong L, Medford A, Uppington K, Robertson J, Witherden I, Tetley T . Expression of functional toll-like receptor-2 and -4 on alveolar epithelial cells. Am J Respir Cell Mol Biol. 2004; 31(2):241-5. DOI: 10.1165/rcmb.2004-0078OC. View