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.