DISENTAGLING IMMUNITY AND TOLERANCE IN CANDIDIASIS
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1
Department of Experimental Medicine and Biochemical Science University of Perugia, Italy
The ability to tolerate Candida albicans, a component of human microbiota, implicates that host defense mechanisms of resistance and tolerance cooperate to limit fungal burden and inflammation at the different body sites. We have disentangled resistance and tolerance components of murine and human C. albicans mucosal infection and have introduced the challenging notion of a disease due to a defective tolerance mechanism. While some degree of inflammation is required for protection at mucosal tissues during the transitional response occurring between the rapid innate and slower adaptive responses, progressive inflammation worsens disease and ultimately prevents pathogen Resistance and tolerance mechanisms were both activated in murine intestinal and vaginal candidiasis through the contribution of innate and adaptive immune responses, involving distinct modules of immunity, IL-22 and Th1/Th17 cells for resistance and IL-10-producing regulatory T cells for tolerance., with a major contribution by the enzyme indoleamine 2,3-dioxygenase 1 (IDO1). IDO1 was responsible for the production of tolerogenic kynurenines, such that replacement therapy with kynurenines restored immunoprotection to murine vaginal candidiasis. In humans, two functional genetic variants in IL22 and IDO1 genes were found to be associated with heightened resistance to recurrent vulvovaginal candidiasis, a disease of unknown origin, and they correlated with increased local expression of IL-22, IDO1 and kynurenines. Thus, IL-22 and IDO1 are crucial in balancing resistance with tolerance to Candida, their deficiencies are risk factors for mucosal infection resulting from transition from symbiont to pathobiont.
Keywords:
Candida albicans,
recurrent vulvovaginal candidiasisy,
IDO1,
IL-22,
Resistance,
tolerance
Conference:
15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013.
Presentation Type:
Abstract
Topic:
Adaptive Immunity
Citation:
De Luca
A,
Carvalho
A,
Iannitti
RG,
Giovannini
G,
Bartolommei
L,
Moretti
S,
Massi Benedetti
C,
Puccetti
M,
Cunha
C and
Romani
L
(2013). DISENTAGLING IMMUNITY AND TOLERANCE IN CANDIDIASIS.
Front. Immunol.
Conference Abstract:
15th International Congress of Immunology (ICI).
doi: 10.3389/conf.fimmu.2013.02.00606
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Received:
12 Jun 2013;
Published Online:
22 Aug 2013.
*
Correspondence:
Dr. Antonella De Luca, Department of Experimental Medicine and Biochemical Science University of Perugia, perugia, Italy, antonelladeluca80@hotmail.it