Obesity selectively disrupts long-lasting type 2 immune cell depots in white adipose tissue

Abstract

White adipose tissue (WAT) has emerged as a tissue-resident niche for immunological memory, but whether this depot function extends to type 2 immune memory and how it is modulated by metabolic disease remains incompletely understood. Here, we show that Nippostrongylus brasiliensis infection, in which the parasite transits and damages the lung, establishes a long-lasting immune cell depot in distal abdominal WAT comprising eosinophils, group 2 innate lymphoid cells (ILC2s), and memory T cells that persists after parasite clearance. Intranasal papain administration recapitulates this depot phenotype, demonstrating that depot formation is a general feature of pulmonary type 2 inflammation rather than a response restricted to live infection. Adoptive transfer of OT-II T cells together with ovalbumin-coated N. brasiliensis larvae confirms that WAT accumulates bona fide antigen-experienced T cells. Diet-induced obesity selectively disrupts depot establishment, while leaving acute lung-stage immune cell recruitment, parasite clearance, and the intrinsic competence of cells that do accumulate largely intact. Despite preserved early lung recruitment, obese mice show exacerbated peri-alveolar tissue damage, consistent with an uncoupling of immune cell infiltration from productive type 2-dependent wound repair. Together, these findings establish WAT as a broadly competent type 2 immunological memory niche, identify obesity as a selective disruptor of depot formation rather than effector function, and provide a cellular framework for the impaired vaccine and infection responses associated with obesity.