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Mycobacteria exploit p38 signaling to affect CD1 expression and lipid antigen presentation by human dendritic cells

Gagliardi, Maria Cristina and Teloni, Raffaela and Giannoni, Federico and Mariotti, Sabrina and Remoli, Maria Elena and Sargentini, Valeria and Videtta, Melissa and Pardini, Manuela and De Libero, Gennaro and Coccia, Eliana Marina and Nisini, Roberto. (2009) Mycobacteria exploit p38 signaling to affect CD1 expression and lipid antigen presentation by human dendritic cells. Infection and immunity, Vol. 77. pp. 4947-4952.

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Official URL: http://edoc.unibas.ch/dok/A6003236

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Abstract

Group I CD1 proteins are specialized antigen-presenting molecules that present both microbial and self lipid antigens to CD1-restricted alpha/beta 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.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Experimental Immunology (De Libero)
UniBasel Contributors:De Libero, Gennaro
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:American Society for Microbiology
ISSN:1098-5522
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:01 Feb 2013 08:46
Deposited On:01 Feb 2013 08:41

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