γδ T Cells Respond Directly to Pathogen-Associated Molecular Patterns

Abstract

γδ T cells recognize unprocessed or non-peptide Ags, respond rapidly to infection, and localize to mucosal surfaces. We have hypothesized that the innate functions of γδ T cells may be more similar to those of cells of the myeloid lineage than to other T cells. To begin to test this assumption, we have analyzed the direct response of cultured human and peripheral blood bovine γδ T cells to pathogen associated molecular patterns (PAMPs) in the absence of APCs using microarray, real-time RT-PCR, proteome array, and chemotaxis assays. Our results indicate that purified γδ T cells respond directly to PAMPs by increasing expression of chemokine and activation-related genes. The response was distinct from that to known γδ T cell Ags and different from the response of myeloid cells to PAMPs. In addition, we have analyzed the expression of a variety of PAMP receptors in γδ T cells. Freshly purified bovine γδ T cells responded more robustly to PAMPs than did cultured human cells and expressed measurable mRNA encoding a variety of PAMP receptors. Our results suggest that rapid response to PAMPs through the expression of PAMP receptors may be another innate role of γδ T cells.

Dual RNA-seq of pathogen and host

“…Likewise, tiling arrays were applied to both in vitro and in vivo grown Listeria monocytogenes (Toledo-Arana et al, 2009) and used to identify sRNAs or novel virulence genes in streptococci (Kumar et al, 2010;Perez et al, 2009;Zheng et al, 2011). In turn, microarrays yielded important insights into the global response of potential mammalian hosts upon cytokine (Zhu et al, 1998) or pathogen-associated molecular pattern (PAMP) stimulation (Hedges et al, 2005;Kerns et al, 2009;Tross et al, 2009), as well as towards diverse bacterial (reviewed in Rappuoli, 2000) or viral infections (Der et al, 1998). Recently, two microarray-based studies reported the response of human epithelial cells to S. Typhimurium infection and found that by secreting effector proteins Salmonella induces pervasive transcriptional reprogramming in the host (Bruno et al, 2009;Hannemann et al, 2013).…”

Mucosal lymphatic-derived γδ T cells respond early to experimental Salmonella enterocolitis by increasing expression of IL-2Rα

“…Also, though it is widely accepted that γδ T cells recognize microbial nonpeptidic phosphorylated molecules [16][17][18] and alkylamines [19,20] in a TCRdependent manner, LPS has not, to our knowledge, been described as a TCR ligand. While we have not precisely determined the mechanism of LPS detection, transcripts encoding many TLRs and other pattern recognition proteins are readily detected in γδ T cells [15,[21][22][23][24][25]. Other groups have shown that TLR agonists have co-stimulatory effects in combination with TCR engagement on γδ T cells, similar in many respects to the priming effect described here [21,25].…”

“…Priming alone does not lead to proliferation unless IL-2 or IL-15 is present, which may vary widely between animals, potentially explaining the inconsistent changes in γδ T cells in the lymphatic fluid within 48-72 hours of Salmonella infection. Priming also leads to a rather restrictive pattern of cytokine production by γδ T cells, reflected mainly in secretion of select chemokines, such as MIP1-α, GM-CSF and RANTES [15]. We have no evidence that prototypic cytokines of inflammatory γδ T cells, such as IFN-γ or TNF-α, are induced by this mechanism in bovine cells (data not shown), although this may be a downstream effect following secondary signals [29].…”

“…The priming event described here is subtle and in some instances many primarily be reflected at only the transcriptional level in PAMP-exposed γδ T cells [15]. Priming alone does not lead to proliferation unless IL-2 or IL-15 is present, which may vary widely between animals, potentially explaining the inconsistent changes in γδ T cells in the lymphatic fluid within 48-72 hours of Salmonella infection.…”

“…Earlier microarray and real time RT-PCR analysis of purified human and bovine γδ T cells stimulated in vitro with E. coli LPS documented increases in mRNAs encoding IL-2Rα and other genes indicative of priming [15], similar to those upregulated in vivo after Salmonella infection. Here we show that IL-2Rα protein upregulation on γδ T cells could be reproduced in vitro with Salmonella serovar Typhimurium LPS alone.…”