Impacts of Salmonella enterica Serovar Typhimurium and Its speG Gene on the Transcriptomes of In Vitro M Cells and Caco-2 Cells

Microfold or membranous (M) cells are specialized intestinal epithelial cells responsible for host immunity. The speG mutant of Salmonella Typhimurium ( S . Typhimurium) is a nonreplicating strain within human cells to be a candidate vaccine vector for interacting with M cells. We conducted this study to identify the genes are differently expressed between in vitro M cells and Caco-2 cells, and to determine whether S . Typhimurium and speG affect the transcriptomes of both cell types. In vitro M cells and Caco-2 cells were infected with wild-type (WT) S . Typhimurium, its Δ speG mutant, or none for 1 h for RNA microarrays; the transcriptomes among the 6 pools were pairwisely compared. Genetic loci encoding scaffold (e.g., HSCHR7_CTG4_4 , HSCHR9_CTG9_35 ), long noncoding RNA, membrane-associated protein ( PITPNB ), neuron-related proteins ( OR8D1 , OR10G9 , and NTNG2 ), and transporter proteins ( MICU2 and SLC28A1 ) were significantly upregulated in uninfected M cells compared with uninfected Caco-2 cells; and their encoding proteins are promising M-cell markers. Significantly upregulated HSCHR7_CTG4_4 of uninfected in vitro M cells were speG -independently downregulated by S . Typhimurium infection that is a remarkable change representing an important but unreported characteristic of M cells. The immune responses of in vitro M cells and Caco-2 cells can differ and reply on speG or not, with speG -dependent regulation of KYL4 , SCTR , IL6 , TNF , and CELF4 in Caco-2 cells, JUN , KLF6 , and KCTD11 in M cells, or speG -independent modulation of ZFP36 in both cells. This study facilitates understanding of the immune responses of in vitro M cells after administering the S . Typhimurium Δ speG mutant as a future vaccine vector.