NK Cells in Mucosal Defense against Infection

Abstract

Conventional natural killer cells (NK cells) provide continual surveillance for cancer and rapid responses to infection. They develop in the bone marrow, emerge as either NK precursor cells, immature, or mature cells, and disperse throughout the body. In the periphery NK cells provide critical defense against pathogens and cancer and are noted to develop features of adaptive immune responses. In the tightly regulated and dynamic mucosal tissues, they set up residency via unknown mechanisms and from sources that are yet to be defined. Once resident, they appear to have the ability to functionally mature dependent on the mucosal tissue microenvironment. Mucosal NK cells play a pivotal role in early protection through their cytolytic function and IFNγ production against bacteria, fungi, viruses, and parasitic infections. This review presents what is known about NK cell development and phenotypes of mucosal tissue resident conventional NK cells. The question of how they come to reside in their tissues and published data on their function against pathogens during mucosal infection are discussed. Dissecting major questions highlighted in this review will be important to the further understanding of NK cell homing and functional diversity and improve rational design of NK cell based therapies against mucosal infection.

Activation of Natural Killer Cells by Probiotics

“…The current understanding of NK development and migration models suggests that NK cells emerge from BM and are a mixture of both mature and immature NK (iNK) cells. 47 …”

“…57 The diversity of the expression of receptors on NK cells may indicate that the tissues are able to regulate the migration of the cells to specific organs such as the gut epithelium. 47 Furthermore, it has been suggested that NK cells in the gut require priming for activation by varying cytokines that include IFN-γ, IL-15, and IL-18. 49 In the gut, iNK cells are primed to the gut mucosa by interacting with CCR7 + CD103 + DCs, resulting in the expression of CCR9.…”

“…3). 47 Therefore, NK cells are stimulated and require several different cytokines to carry out and activate other nearby cells. The addition of probiotics helps to stimulate specific cytokines that regulate NK cell responses and secretions, leading to a form of a cross talk between innate immunity and adaptive immunity.…”

PILRα binds an unknown receptor expressed primarily on CD56bright and decidual-NK cells and activates NK cell functions

“…Nevertheless, the full spectrum of NK cell receptors and ligands that control NK cell activity is unknown. In particular, the identities of the ligands recognized by some of the activating NK cell receptors remains largely uncharacterized [2][4][30]. The identification of new NK cell receptors and ligands will contribute to the broad understanding of NK cell function and also potentially provide added value to establish new therapeutics in the field of cancer, autoimmunity and infectious diseases.…”

“…NK cells express a vast combinatorial array of receptors that can activate or inhibit NK-mediated cytotoxicity and cytokine secretion, in response to oncogenic transformation, bacterial, fungal and viral infections [1][2]. When encountered with target cells, the decision to kill or spare the target cells is determined by a balance of signals delivered by these receptors, which recognize a variety of ligands on the target cells [3][4].…”