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Infection and Immunity, November 2009, p. 4947-4952, Vol. 77, No. 11
0019-9567/09/$08.00+0     doi:10.1128/IAI.00607-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Mycobacteria Exploit p38 Signaling To Affect CD1 Expression and Lipid Antigen Presentation by Human Dendritic Cells{triangledown}

Maria Cristina Gagliardi,1 Raffaela Teloni,1 Federico Giannoni,1 Sabrina Mariotti,1 Maria Elena Remoli,1 Valeria Sargentini,1 Melissa Videtta,2 Manuela Pardini,1 Gennaro De Libero,3 Eliana Marina Coccia,1 and Roberto Nisini1*

Dipartimento di Malattie Infettive, Parassitarie e Immunomediate, Istituto Superiore di Sanità, Roma, Italy,1 Dipartimento di Medicina Interna, Sapienza Università di Roma, Roma, Italy,2 Experimental Immunologie, Departement Forschung Universitätsspital Basel, Basel, Switzerland3

Received 29 May 2009/ Accepted 11 August 2009

Group I CD1 proteins are specialized antigen-presenting molecules that present both microbial and self lipid antigens to CD1-restricted {alpha}/β T lymphocytes. The production of high levels of gamma interferon and lysis of infected macrophages by lipid-specific T lymphocytes are believed to play pivotal roles mainly in the defense against mycobacterial infections. We previously demonstrated that Mycobacterium tuberculosis and bacillus Calmette-Guérin (Mycobacterium bovis BCG) induce human monocytes to differentiate into CD1– dendritic cells (DC), which cannot present lipid antigens to specific T cells. Here, we show that in human monocytes mycobacteria trigger phosphorylation of p38 mitogen-activated protein kinase to inhibit CD1 expression in DC derived from infected monocytes. Pretreatment with a specific p38 inhibitor renders monocytes insensitive to mycobacterial subversion and allows them to differentiate into CD1+ DC, which are fully capable of presenting lipid antigens to specific T cells. We also report that one of the pathogen recognition receptors triggered by BCG to activate p38 is complement receptor 3 (CR3), as shown by reduced p38 phosphorylation and partial reestablishment of CD1 membrane expression obtained by CR3 blockade before infection. In conclusion, we propose that p38 signaling is a novel pathway exploited by mycobacteria to affect the expression of CD1 antigen-presenting cells and avoid immune recognition.

* Corresponding author. Mailing address: Dipartimento Malattie Infettive, Parassitarie e Immunomediate, Istituto Superiore di Sanità, Viale Regina Elena, 299, 00161 Roma, Italy. Phone: 39 06 49902659. Fax: 39 06 49902886. E-mail: roberto.nisini{at}iss.it

{triangledown} Published ahead of print on 31 August 2009.

Editor: J. L. Flynn

Infection and Immunity, November 2009, p. 4947-4952, Vol. 77, No. 11
0019-9567/09/$08.00+0     doi:10.1128/IAI.00607-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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