Microsporidia, which belong to the kingdom Fungi, are important opportunistic pathogens in HIV-infected populations and organ transplant recipients that are often associated with a broad range of symptoms, such as diarrhea, nephritis, and encephalitis. Natural infection occurs via the oral route, and as a consequence, gut immunity plays an important role in restricting the dissemination of these pathogens. Studies from our laboratory have reported that the pathogens induce a rapid intraepithelial lymphocyte (IEL) response important for host protection. Although mucosal dendritic cells (DC) are likely involved in triggering an antigen-specific IEL response, the specific subset(s) responsible has yet to be identified. Toward this goal, we demonstrate a very important role for mucosal CD11b ؊ CD8 ؉ DC in the initiation of an antigen-specific IEL in vivo. Effectively, after Encephalitozoon cuniculi infection, CD11b؊ CD8 ؉ DC were activated in the lamina propria (LP) and acquired the ability to process retinoic acid (RA). However, this subset did not produce interleukin 12 (IL-12) but upregulated CD103, which is essential for migration to the mesenteric lymph nodes (MLN). Interestingly, CD103؉ CD11b ؊ CD8 ؉ DC in the MLN, in addition to processing RA, also secreted IL-12 and were responsible for gut imprinting specificity on mucosal CD8 T cells. To the best of our knowledge, this is the first report describing the importance of MLN CD103 ؉ CD11b ؊ CD8 ؉ DC isolated from infected animals in the generation of an IEL response against a live pathogen. Human microsporidiosis is an opportunistic infection caused by a spore-forming unicellular eukaryote related to fungi, most specifically zygomycetes (1). Of the 14 species infecting humans, Enterocytozoon bieneusi, Encephalitozoon intestinalis, Encephalitozoon cuniculi, and Encephalitozoon hellem are the most common (2). The incidence of microsporidia in HIV patients remains very high, especially in places such as Russia, Venezuela, and Thailand, where microsporidium prevalence ranges from 13 to 80% (3-5). Lately, it has been reported that microsporidial infections can cause complications in non-HIV populations, especially those receiving organ transplants (6-9). In a very recent study, Kotkova et al. demonstrated that microsporidiosis was probably a latent infection, which could reactivate in an immunocompromised situation, further highlighting the importance of studying the immune response against this ubiquitous pathogen (10). An experimental murine model using E. cuniculi mimics the human infection and has commonly been used to investigate the host immune response (11). Most microsporidial species are acquired by ingesting contaminated water or food, and the gut immunity to this pathogen still remains cryptic. Intraepithelial lymphocytes (IEL) form one of the first lines of immune defense in the gut tissue (12), and their protective role against various pathogens has been reported (13-16). Previous studies from our laboratory demonstrated early and rapid induction of th...

Microsporidia are a group of pathogens, which can pose severe risks to the immunocompromised population such as HIV infected individuals. The expertise to diagnose these pathogens is limited and therefore their prevalence is believed to be much higher than what is currently known. In a mouse model of infections, it has been reported that CD8 T cells are the primary effector cells responsible for protecting the infected host. As the infection is acquired via per-oral route, CD8 T cells in the gut compartment apparently act as a first line of defense against the pathogens. Thus, generation of a robust CD8 T cell response that exhibits polyfunctional ability is critical for host survival. In this review, we describe the effector CD8 T cells generated during microsporidial infection and underline the factors that may be essential for the elicitation of protective immunity against this understudied but significant pathogen. Overall, this review will highlight the necessity for a better understanding of the development of the CD8 T cell response in gut associated lymphoid tissue (GALT) and provide some insights into therapies that may be used to restore defective CD8 T cell functionality in an immunocompromised situation.