Innate and adaptive immune response to C. albicans
Research area: Cellular Immunology
Group leaders: Federica Sallusto
Status: In progress
C. albicans is part of the human commensal flora and poses no risk to healthy individuals. However, under certain circumstances it colonizes the vagina and develops into recurrent infection, affecting 70% of the female population. It is not known why this infection develops and how the immune system can control the pathogen in the vaginal tissue. Earlier studies showed that the IL-17 axis is a crucial part of the host defense mechanism against fungal infections in other tissues. T cells and gd T cells were identified as being the major source of IL-17 in response to C. albicans. By using a mouse model of vaginal candidiasis, we found that protection in the vaginal tissue is not only dependent on T cells but it requires the presence of IL-22-producing innate lymphoid cells as well. Mice either deficient of IL-22 producing T cells (Rag1–/–) or IL-22 producing ILCs (Rorc–/–, Il23a–/–) are unable to control candida infection. Interestingly, mice lacking ILCs are more susceptible and succumb earlier to candida infection than mice lacking only T cells. This observation reveals a so far undescribed interaction between the innate and adaptive arm of the immune system in the vaginal tissue, similar to the one observed in the gut mucosa. ILCs promptly produce IL-22 upon infection and most likely slow down the colonization of the vagina by candida. This first, antigen unspecific wave of immune response is followed by the activation of IL-22 producing T cells which ultimately leads to pathogen clearance.
This work is done in collaboration with Burkhard Becher, University of Zurich (CH).