2. The role of SAT in induction of a protective immune response against pathogens
The skin serves as the primary defense against pathogen invasion. It provides both a physical barrier and an intrinsic warning system to trigger innate and adaptive immune responses when the physical barrier is breached. The role of epidermal/dermal leukocytes, keratinocytes, and other non-leukocyte populations in antimicrobial defense has been well investigated. In contrast, the contribution of underlying SAT to this process remains largely unexplored (53).
One avenue through which adipocytes can participate in antimicrobial defense is through the release of soluble mediators. Adipokines released by adipocytes, as shown in a series of mouse studies, have the ability to recruit immune cells to infection sites and modulate their effector functions (54, 55). Leptin, a well-characterized adipokine known for its role in hunger regulation, also exhibits immunomodulatory properties, contributing to antimicrobial immune responses (56-58). Studies on leptin/leptin receptor-deficient mice have revealed increased susceptibility to viral or bacterial infections (59-61). In obese individuals, elevated blood levels of leptin lead to leptin resistance, which in turn induces a reduced type I interferon (IFN) response and increased susceptibility to viral infection (62, 63).
Adipocytes are also a major secretor of cathelicidins, short cationic antimicrobial peptides (30, 64) (Fig 4). Obese animals produce fewer cathelicidins, thereby contributing to compromised infection control (65) (Table 1). Beyond adipocytes, one finding that links AT to the immune system is that WAT harbors a significant number of resident memory T-cells. This population can be rapidly reactivated to provide protection against pathogens (66). Studies in mice and humans indicate that obesity is associated with impaired memory T-cell responses and reduced natural killer cell cytotoxicity (67-76). Furthermore, systemic viral infections have been shown to alter SAT immune-metabolic functions in mice, notably by inducing AT expansion (77-79). Unraveling the specific mechanisms through which SAT contributes to immune defense may open avenues for therapeutic interventions targeting both metabolic and immunologic aspects, with potential implications for preventing and managing infectious diseases.