AIRE Deficiency Affects The Function Of Macrophage In Response To Candida Albicans

Autoimmune regulator is the transcription factor expressed in medullary epithelial cells where this gene is responsible for the articulation and presentation of different specific tissue restricted antigens and subsequent maturation and negative selection of T-lymphocytes.AIRE also help in development of regulatory T cells.Mutation in AIRE gene result in multiple organs autoimmune disease and mucocutaneous candidiasis,also the APECED patients develop antibodies to different glandular organs include testis,ovaries and thyroid etc.AIRE gene also expressed extra thymically in different sites like in secondary lymphoid organs and in monocyte and macrophages,where it helps in deletion of T cells which get escaped from the central tolerance in the thymus,AIRE can be used in therapies to cure Graft versus host diseases.Several experiments have shown that extra-thymic expression of AIRE may play a crucial role in local immune responses by regulating the expression of PRR and MHC on Antigen presenting cells.AIRE deficient individuals are more prone to candidiasis.Body responding to Candida albicans through innate immunity equipped mainly with Macrophages and dendritic cells,in this research work we tried to insight and find out the effects of AIRE gene on macrophages response to Candida albicans,by exposure of macrophage derived from AIRE knockout mice to Candida albicans in vitro,and establishment of Candida albicans infected AIRE knockout mice model.Our results concluded that,1.Expression of M1 associated molecules like IL-6 and i NOS along with Candida albicans associated PRR like Dectin-1 and TLR-2 were significantly lower in AIREKO mice peritoneal macrophages response to the Candida albicans in vitro.2.Candida albicans infection was more severe in AIRE-knockout mice ranging from Lassitude and lethargy along with high infiltration of candida in vital organs like heart,kidney and spleen.And the expression of M1 associated molecules in macrophage of AIRE-knockout mice,including i NOS and IL-1?,were lower than those in wild type mice.The survival rate significantly decreased in AIRE knockout mice.This study indicates that AIRE could influence the macrophage response to Candida albicans and those AIRE-KO infected mice are more vulnerable to Candida albicans infection.The results will help us to understand the reason of patients with AIRE mutation susceptible to Candida albicans.