Yeasts: neglected pathogens.
BACKGROUND
Current research on Crohn's disease (CD) concerns molecular events related to loss of tolerance to microbes that could trigger or maintain inflammation in genetically susceptible individuals. CD is also associated with antimicrobial antibodies, including the antibodies we described against yeast oligomannosides (ASCA). This prompted us to investigate a role for another yeast, Candida albicans, a very common commensal of the human digestive tract and an important opportunistic pathogen.
It has been revealed that the major oligomannose epitopes supporting ASCA are expressed by C. albicans in human tissues, suggesting that C. albicans is the immunogen for ASCA. This link has been reinforced by the demonstration that novel serological markers of CD (ALCA and ACCA), consisting of antibodies against chitin and glucan (two components of the C. albicans cell wall), are also generated during C. albicans infection. Mycological investigation of families with multiple cases of CD shows that patients with CD and their healthy relatives are colonized with C. albicans more commonly than control families. In healthy relatives, C. albicans colonization correlates with ASCA levels, whereas the onset of CD is associated with ASCA stability and is independent of the C. albicans intestinal load. Experimental studies show that chemically-induced colitis promotes C. albicans colonization in mice. In turn, C. albicans colonization generates ASCA, increases inflammation, histological scores and pro-inflammatory cytokine expression.


CONCLUSIONS
Current investigations focus on interactions of TLRs and lectins with yeast epitopes that differently polarize the immune response to C. albicans cell wall glycans, which are the targets of an 'excessive' adaptive response associated with CD.
Poulain
Daniel
D
Université Lille Nord de France, UDSL, CHU Lille, Inserm U799, Inserm U795, Lille, France. dpoulain@univ-lille2.fr
Sendid
Boualem
B
Standaert-Vitse
Annie
A
Fradin
Chantal
C
Jouault
Thierry
T
Jawhara
Samir
S
Colombel
Jean-Frederic
JF
D000818:Animals; D000908:Antibodies, Fungal / Q000276:immunology; D002176:Candida albicans / Q000276:immunology*; D002177:Candidiasis / Q000097:blood / Q000175:diagnosis / Q000382:microbiology; D002473:Cell Wall / Q000378:metabolism; D003424:Crohn Disease / Q000097:blood / Q000175:diagnosis / Q000382:microbiology*; D006801:Humans; D051379:Mice; D012441:Saccharomyces cerevisiae / Q000276:immunology
D000908:Antibodies, Fungal