The interaction between invariant Natural Killer T cells and the mucosal microbiota

Abstract

SummaryThe surface of mammalian bodies is colonized by a multitude of microbial organisms, which under normal conditions support the host and are considered beneficial commensals. This requires, however, that the composition of the commensal microbiota is tightly controlled and regulated. The host immune system plays an important role in the maintenance of this microbiota composition. Here we focus on the contribution of one particular immune cell type, invariant Natural Killer T (iNKT) cells, in this process. The iNKT cells are a unique subset of T cells characterized by two main features. First, they express an invariant T-cell receptor that recognizes glycolipid antigens presented by CD1d, a non-polymorphic major histocompatibility complex class I-like molecule. Second, iNKT cells develop as effector/memory cells and swiftly exert effector functions, like cytokine production and cytotoxicity, after activation. We outline the influence that the mucosal microbiota can have on iNKT cells, and how iNKT cells contribute to the maintenance of the microbiota composition.

NKT and NKT-like Cells in Autoimmune Neuroinflammatory Diseases—Multiple Sclerosis, Myasthenia Gravis and Guillain-Barre Syndrome

“…iNKT cells recognise α-galactosylceramide (α-GalCer) and some similar lipid-derivatives such as microbial α-glycuronylceramides or human self-antigen isoglobotrihexosylceramide [3]. Moreover, they recognise various microbial antigens derived from microorganisms such as M. tuberculosis, B. burgdorferi, Aspergillus sp., and S. pneumoniae [4]. Type II NKT are activated by the CD1d-sulfatide complex, sulfatide is widely expressed in the kidney, liver, and central nervous system with sulfatide being one of the myelin sheath components [5,6].…”

License to Kill: When iNKT Cells Are Granted the Use of Lethal Cytotoxicity

“…All iNKT cells recognize and are potently activated by α-galactosylceramide (α-GalCer), a bacteria-derived glycolipid originally discovered in marine sponges [1]. Since then, several microbial antigens have been discovered both in pathogen and commensal microbes [7][8][9][10][11][12][13][14]. On the other hand, it has been demonstrated that the iNKT cell activation by self-antigens is important during thymic selection [1,15,16], infections [17][18][19][20], and autoimmune diseases [21].…”

“…This is achieved thanks to the capacity of iNKT cells to recognize microbial and microbe-induced self-antigens, as well as being activated by innate and cytokine signals, such as IL-12 and TLRs [50][51][52][53][54]. Given this, iNKT cells are important in the control of homeostasis in many mucosal tissues, like the intestine and lung, but also in the response against pathogens [9,[50][51][52][53][54][55][56]. More specifically, iNKT cells participate in the response against infectious agents mainly by mediating the activation of other immune cell types through the release of interferon (IFN) gamma [9,[50][51][52][53][54][55].…”

On invariant T cells and measles: A theory of “innate immune amnesia”

“…i NKT cells detect glycolipid Ags, including those derived from pathogens, presented within the hydrophobic pocket of CD1d [ 38 – 40 ] ( Fig 2A ). The antimicrobial properties of these invariant T ( i T) cells are owed to their tremendous immunomodulatory and cytolytic activities [ 32 , 41 – 43 ].…”