Furthermore, the data presented here illustrate that this three different types of ILCs have very different responses to HSV-1 contamination and control of HSV-1 replication. type 3 ILC-deficient mice were used to gain insights into the effects of the ILCs on the outcome of ocular HSV-1 contamination. No significant differences were found on comparison with similarly infected wild-type mice or on comparison of the three strains of deficient mice in terms of computer virus replication in the eyes, levels of corneal scarring, latency-reactivation in the trigeminal ganglia, or T-cell exhaustion. Although there were no significant differences in the survival rates of infected ILC-deficient mice and wild-type mice, there was significantly reduced survival of the infected type 1 or type 3 ILC-deficient mice compared with type Blonanserin 2 ILC-deficient mice. Adoptive transfer of wild-type T cells did not alter survival or any other parameters tested in the infected mice. Our results indicate that type 1, 2, and 3 ILCs respond differently to HSV-1 contamination and that the absence of type 1 or type 3, but not type 2, ILCs affects the survival of ocularly infected mice. IMPORTANCE In this study, we investigated for the first time what functions, if any, innate lymphoid cells (ILCs) play in HSV-1 contamination. Analysis of isolated ILCs revealed that all three subtypes could be infected with HSV-1 but that they were resistant to replication. The Blonanserin expression profiles of HSV-1-induced cytokines/chemokines and cellular and viral genes Blonanserin differed among the infected type 1, 2, and 3 ILCs analysis of the effects of ILC deficiency. ILCs are conserved in mice and humans (4, 10). They have been shown to play important functions in host defense, metabolic homeostasis, and tissue repair and can contribute to inflammatory diseases, such as asthma and colitis (19). Group 1 ILCs include type 1 ILCs and natural killer (NK) cells (3, 20). Similar to NK cells, type 1 ILCs function in the immune response to intracellular pathogens, including protozoan parasites, bacteria, and viruses (2, 21,C23). Use of the T-bet?/? type 1 ILC-deficient mouse model has shown that type 1 ILCs limit replication in the intestine (24). Recently, it has been shown that human type 1 ILCs can be subcategorized into CD4+ and CD4? populations. CD4+ type 1 ILCs were efficiently infected by human immunodeficiency computer virus type 1 (HIV-1) and contamination is usually impaired in RoraFloxIL7RCre type 2 ILC-deficient mice (28), and the absence of major histocompatibility complex class II (MHC-II) reduced the ability of the type 2 ILCs to efficiently control helminth contamination (29). In contrast, type 2 ILC deficiency had no effect on clearance of (28). Type 2 ILCs are the predominant ILC populace in human and mouse lungs and are key initiators of allergen- and non-allergen-induced type 2 inflammation, as well as acting to promote airway tissue repair (1, 2, 30). Brain is also rich in type 2 ILCs, and it has been shown that mucosal neurons regulate type 2 inflammation by Blonanserin releasing neuromedin U (NMU), a neuropeptide that directly activates type 2 ILCs (31,C33). Type 3 ILCs are major regulators of inflammation and contamination at mucosal barriers. Although they are present CDK2 in small numbers in the intestinal tract, they have been shown to be important for controlling contamination (34, 35), thereby providing defense against intestinal infections by various pathogenic bacteria, such as (36, 37), and fungi (2). Studies of mice with intact T cells have indicated that type 3 ILCs can have redundant functions in protection against enteropathogenic bacteria.