Abundance of single filamentous bacteria, and expression of differentiated Th17 cells, their signature cytokine IL-17 A, and retinoic acid receptor are predictive of poor rotavirus vaccine take.

Abstract

Single filamentous bacteria (SFB) have been shown to prevent murine rotavirus (RV) and other mammalian enteric infections, independent of type I and II interferons, by promoting adaptive and innate immunity through differentiation of intestinal Th17 cells, production of immunoglobulin A and retinoic acid receptor (RAR) signaling. Here, we assessed whether the abundance of the bacterium at the time of oral RV vaccination would impede the vaccine performance. Stool samples were collected from infants a week after RV vaccination to determine vaccine shedders (n = 20) and non-shedders (n = 20). The abundance of SFB and expression of Cathepsin L (CTSL, a biomarker for differentiated Th17 cells), cytokines 17 A and IL-22, and retinoic acid receptor (RAR) were assayed using quantitative PCR. The abundance of SFB was significantly high in non-shedders compared to vaccine shedders, p = 0.042, and correlated negatively with vaccine virus shedding load (R = - 0.69). The expression of CTSL was increased 3.5-fold in non-shedders compared to vaccine shedders, p = 0.035. Similarly, the expression of IL-17 A and IL-22 was increased 8.5- and 12-fold, respectively, in non-shedders versus shedders. The expression of RAR was also consistent with the abundance of SFB, as it increased 5.9-fold in non-shedders compared to vaccine shedders, p = 0.034. Logistic regression analysis indicated that Infants possessing increased abundance of SFB were less likely to shed the vaccine in stool samples (OR = 0.31, 95% CI = 0.102-0.962), p = 0.043. Taken together, our observations suggest that the abundance of SFB at the time of vaccination may impede the oral RV vaccine take in the study population.