Innate lymphocytes: Role in alcohol-induced immune dysfunction

Abstract

Alcohol use is known to alter the function of both innate and adaptive immune cells, such as neutrophils, macrophages, B cells, and T cells. Immune dysfunction has been associated with alcohol-induced end-organ damage. The role of innate lymphocytes in alcohol-associated pathogenesis has become a focus of research, as liver-resident natural killer (NK) cells were found to play an important role in alcohol-associated liver damage pathogenesis. Innate lymphocytes play a critical role in immunity and homeostasis; they are necessary for an optimal host response against insults including infections and cancer. However, the role of innate lymphocytes, including NK cells, natural killer T (NKT) cells, mucosal associated invariant T (MAIT) cells, gamma delta T cells, and innate lymphoid cells (ILCs) type 1–3, remains ill-defined in the context of alcohol-induced end-organ damage. Innate-like B lymphocytes including marginal zone B cells and B-1 cells have also been identified; however, this review will address the effects of alcohol misuse on innate T lymphocytes, as well as the consequences of innate T-lymphocyte dysfunction on alcohol-induced tissue damage.

A Pathogenic Role of Non-Parenchymal Liver Cells in Alcohol-Associated Liver Disease of Infectious and Non-Infectious Origin

“…This relationship is now firmly established, and severe ALD is well-known to be an immunocompromised state, rendering patients highly vulnerable to overwhelming bacterial infections [29][30][31]. As the first line of defense, the innate arm of the host immunity is the vanguard to bacterial pathogens [32], and this may reflect the extensive research efforts in characterizing the dysfunctional innate immunity in ALD [33,34]. Notably, increasing evidence reveals the key role of adaptive immunity in the antimicrobial armamentarium [35], and particularly, T cells are thought to be central [36].…”

“…Recent evidence has described the role of unconventional T-cell populations in the deficient antimicrobial response in ALD, including the mucosa-associated invariant T (MAIT) cells, CD1-restricted T cells, and γδ T cells that utilize MR1, CD1 molecules, and BTN/BTNL molecules to respond to lipid, metabolic, or other antigenic stimuli [33]. We have focused on the MAIT compartment: these innate-like CD161-positive T cells are fundamental to the immune control of gut microbiota, bacterial infection, and inflammatory diseases.…”