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Interleukin (IL)-18, a member of the IL-1 family of alarmins, is abundantly released in the lungs following influenza A (IAV) infections yet its role in orchestrating the local adaptive immune response remains ill defined. Through genetic disruption of the IL-18 receptor, we demonstrate that IL-18 not only promotes pulmonary T H 1 responses but also influences regulatory T cells (T REG ) function in the infected lungs. As the response unfolds, T REG cells accumulating in the lungs express Helios, T-bet, CXCR3, and IL-18R1 and produce interferon γ in the presence of IL-12. During IAV, IL-18R1 is required for T REG cells to control T H 17, but not T H 1, responses and promote a return to lung homeostasis, revealing a novel mechanism of selective suppression. Moreover, this observation was not limited to the lungs, as skin-localized T REG cells require an IL-18 signal to specifically suppress IL-17A production by T H 17 and γδ T cells in a model of chronic cutaneous Leishmania major infection. Overall, these results uncover how IL-18 orchestrates the tissue adaptation of T REG cells to selectively favor T H 1 over T H 17 responses during T H 1-driven immune responses and provide a novel perspective into how IL-18 dictates the immune response during viral and parasitic infections., (Copyright © 2023. Published by Elsevier Inc.)

CD4 + Foxp3 + regulatory T (T REG ) cells are critical mediators of peripheral tolerance and modulators of immune responses. Functional adaptation of T REG cells, through acquisition of secondary transcription factors is critical for their effector differentiation towards local inflammatory stimuli including infections. The drivers and consequences of this adaptation of T REG cell function remain largely unknown. Using an unbiased screen, we identified receptors of the IL-1 family controlling the adaptation of T REG cells. Through respiratory infection models, we show that the IL-33 receptor (ST2) and the IL-1 receptor (IL1R1) selectively identify stable and unstable T REG cells at mucosal surfaces, respectively. IL-33, not IL-1, is specifically required for maintaining the suppressive function of T REG cells. In the absence of ST2, T REG cells are prone to lose Foxp3 expression and acquire RORγT and IL1R1, while, in the absence of IL-1R1, they maintain Foxp3 expression and resist the acquisition of a Th17 phenotype. Finally, lack of IL-1 signalling enhances the accumulation of ST2 + T REG over pro-inflammatory T REG cells in a Cryptococcus neoformans infection. These observations show that IL-1 and IL-33 exert opposing functions in controlling the functional adaptation of T REG cells, ultimately dictating the dynamics of adaptive immunity to pathogens.

Homeostasis is a fundamental principle of biological systems. A paradigm of immune homeostasis is the remarkably constant number of naive T and B lymphocytes in the body that continuously circulate through the secondary lymphoid organs to maximize immune surveillance. Whether the dynamics and distribution of the systemic naive lymphocyte pool is affected following organ-specific infection is not known. Here we show that, following infection of mice with an enteric helminth, naive T and B lymphocytes accumulate in the T helper type 2-reactive mesenteric lymph node while they are concurrently depleted from non-draining peripheral lymph nodes. This systemic redistribution of naive lymphocytes is sustained into the chronic phase of the infection, requires lymphotoxin beta receptor-dependent signals and is associated with a reduced ability of parasitized animals to mount antigen-specific cellular and humoral immune responses to heterologous immunization or infection at peripheral sites. Our data suggest that the function of the homeostatic naive lymphocyte pool can be modulated by its systemic distribution following infection and may provide a novel concept underlying compromised immune responsiveness at peripheral sites in helminth-infected individuals.

Overall the 1976 Festival of American Folklife was a highly successful affair both from a cultural and environmental health standpoint. Although a number of health-related problems arose on a day-to-day basis, close surveillance and prompt action on the part of the onsite sanitarian made it possible to secure early resolution of them with no ill effects among either visitors or the Festival staff. Logistically, planning and conducting of the comprehensive Smithsonian Institute (SI) food operations involving 50 different ethnic groups was an accomplishment worthy of note. Even more important, however, was the fact that during the entire time the Government Services, Inc. and SI food service operations were in progress, there was not a single case of foodborne illness associated with foods and beverages served to an estimated 500,000 persons onsite. This was in large measure due to the excellent cooperative assistance furnished by health agency personnel in the District of Columbia and the surrounding counties in Maryland and Virginia. These personnel inspected the many food establishments within their jurisdictions which served as sources for foods served at the Festival. All individuals and groups assisting directly or indirectly with this aspect of the Festival may justly be proud of the achievement.