Abstract
Since innate lymphoid cells (ILCs) have been found to play a role in the immune response to helminth parasites in rodents, we sought to determine their role in human helminth infection. By developing multicolor flow cytometry-based methods to identify and enumerate circulating ILCs and their subsets, we were able to identify a subset of cKit+ ILCs defined as Lineage (Lin)−/CD45+/cKit+/CD127+ that were significantly expanded in the filarial-infected individuals (p = 0.0473) as were those cKit+ ILCs that produced IL-13. Additionally, the frequency of these cKit+ ILCs correlated with the frequency of IL-17 producing CD4+ T cells (Th17 cells; p = 0.025). To investigate the function of cKit+ ILCs, sorted, highly purified human ILCs were subjected to transcriptional profiling by RNAseq and compared to appropriate control cells. These cKit+ ILCs expressed TLRs, a broad range of cytokines/cytokine receptors and MHC Class II molecules suggesting that these ILCs sense pathogens independent of other cell types. Functional analysis revealed expanded cKit+ ILC-specific transcription and ILC-specific microRNA precursors.
Highlights
Innate lymphoid cells (ILCs) are identified by their lack of cell lineage markers associated with T cells, B cells, dendritic cells, monocyte/macrophages, and granulocytes, and their expression of CD127 (IL-7Ra), among others [1,2,3,4]
While there was a modest increase in the frequency of total ILCs in Fil+ individuals, there was a statistically significant,2-fold increase (p = 0.0473) in the frequency of the cKit+ ILCs in the Fil+ (geometric mean [GM] frequency = 0.195 (Figure 1B) compared to the frequencies found in NL (GM = 0.096; range 0.0029–0.0369)
Because this cKit+ ILC population is largely comprised of ILC2 and ILC3 subsets and because filarial infection has been associated with increases in CD4+ Th2-like cells, we assessed the frequencies of IL13+cKit+ ILCs in all donors (Figure 1C and Figure 1A for a representative flow diagram)
Summary
Innate lymphoid cells (ILCs) are identified by their lack of cell lineage markers associated with T cells, B cells, dendritic cells, monocyte/macrophages, and granulocytes, and their expression of CD127 (IL-7Ra), among others [1,2,3,4]. ILC subsets can be identified by expression of particular surface markers, with ILC2s and ILC3s expressing cKit (or CD117) and ILC2s expressing ST2 (IL-33R) and CRTH2, for example [5]. ILCs, ILC2s in mice, respond to IL-25 and IL-33 produced from barrier-associated cells by making IL-13 and IL-5 and, to a lesser extent IL-4, which in turn drive a Th2 response [1,2,3]. This family of innate cells has been identified in human tissues and peripheral blood [6]. ILCs have not yet been evaluated either in the context of tissue invasive helminths nor in other human parasitic infections
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
