Group 1 innate lymphoid cells in Toxoplasma gondii infection

Abstract

Innate lymphoid cells (ILCs) are a group of lymphocytes that carry out important functions in immunity to infections and in organ homeostasis at epithelial barrier surfaces. ILCs are innate immune cells that provide an early source of cytokines to initiate immune responses against pathogens. Cytotoxic ILCs (i.e. conventional (c)NK cells) and several subsets of helper-like ILCs are the major branches of the ILC family. Conventional NK cells and group 1 ILCs share several characteristics such as surface receptors and the ability to produce IFN-γ upon activation, but they differ in their developmental paths and in their dependence on specific transcription factors. Infection of mice with the intracellular parasite Toxoplasma gondii is followed by a strong Th1-mediated immune response. Previous studies indicate that NK1.1 cells contribute to the production of IFN-γ and TNF and cytotoxicity during acute T. gondii infection. Upon oral infection, the parasite infects intestinal enterocytes, and within the lamina propria, innate immune responses lead to initial parasite control although the infection disseminates widely and persists long-term in immune privileged sites despite adaptive immunity. Upon parasite entry into the small intestine, during the acute stage, ILC1 produce high levels of IFN-γ and TNF protecting barrier surfaces, thus essentially contributing to early parasite control. We will discuss here the role of innate lymphocytes during T. gondii infection in the context of the only recently appreciated diversity of ILC subsets.

Innate Lymphoid Cells in Protection, Pathology, and Adaptive Immunity During Apicomplexan Infection

“…Even though the ILC classification was recently established to define the innate immune cells of lymphoid lineage, the importance of ILC function for control of T. gondii infection has been investigated for many years (4, 34) (Figure 2). Infection with T. gondii begins after ingestion of oocysts from cat feces or bradyzoite containing tissue cysts from undercooked meat (4, 8).…”

Innate lymphoid cells, mediators of tissue homeostasis, adaptation and disease tolerance

“…However, unlike cNK cells, ILC1 are entirely dependent on T‐bet, they do not contribute significantly to cell‐mediated cytotoxicity in classical assays and they lack the expression of class I MHC‐specific inhibitory receptors (ie, CD94/NKG2A, Ly49, and KIR). Intestinal ILC1 vigorously respond to interleukin (IL)‐12 and produce interferon (IFN)‐γ and tumor necrosis factor (TNF) in response to infection with the intracellular pathogen Toxoplasma gondii . Early immunity to T. gondii infection was impaired in the absence of ILC1 while transfer of ILC1 into lymphopenic mice enhanced resistance to T. gondii …”

The role of host autophagy machinery in controllingToxoplasmainfection

“…In turn they will activate an adaptive immune response mediated by B and T lymphocytes [9] through the action of pro-inflammatory cytokines such as IL-12 [10]. Innate lymphoid cells such as Natural Killer cells are also critical to license antigen-presenting cells and produce soluble factors such as interferon gamma (IFN-γ) that contribute to parasite control [11]. Ultimately, various mechanisms of cell-autonomous immunity triggered by CD8 T cell activity and Th1-polarized CD4 T cell responses are important for parasite control [12], as well as to some extent the humoral response through B cells [13].…”