Innate Immune Recognition of Yersinia pseudotuberculosis Type III Secretion

Specialized protein translocation systems are used by many bacterial pathogens to deliver effector proteins into host cells that interfere with normal cellular functions. How the host immune system recognizes and responds to this intrusive event is not understood. To address these questions, we determined the mammalian cellular response to the virulence-associated type III secretion system (T3SS) of the human pathogen Yersinia pseudotuberculosis. We found that macrophages devoid of Toll-like receptor (TLR) signaling regulate expression of 266 genes following recognition of the Y. pseudotuberculosis T3SS. This analysis revealed two temporally distinct responses that could be separated into activation of NFκB- and type I IFN-regulated genes. Extracellular bacteria were capable of triggering these signaling events, as inhibition of bacterial uptake had no effect on the ensuing innate immune response. The cytosolic peptidoglycan sensors Nod1 and Nod2 and the inflammasome component caspase-1 were not involved in NFκB activation following recognition of the Y. pseudotuberculosis T3SS. However, caspase-1 was required for secretion of the inflammatory cytokine IL-1β in response to T3SS-positive Y. pseudotuberculosis. In order to characterize the bacterial requirements for induction of this novel TLR-, Nod1/2-, and caspase-1-independent response, we used Y. pseudotuberculosis strains lacking specific components of the T3SS. Formation of a functional T3SS pore was required, as bacteria expressing a secretion needle, but lacking the pore-forming proteins YopB or YopD, did not trigger these signaling events. However, nonspecific membrane disruption could not recapitulate the NFκB signaling triggered by Y. pseudotuberculosis expressing a functional T3SS pore. Although host cell recognition of the T3SS did not require known translocated substrates, the ensuing response could be modulated by effectors such as YopJ and YopT, as YopT amplified the response, while YopJ dampened it. Collectively, these data suggest that combined recognition of the T3SS pore and YopBD-mediated delivery of immune activating ligands into the host cytosol informs the host cell of pathogenic challenge. This leads to a unique, multifactorial response distinct from the canonical immune response to a bacterium lacking a T3SS

Sedentary time of university students before and during the COVID-19 pandemic: Risk groups and pre-pandemic predictors using cross-sectional and longitudinal data

Background!#!The present study aimed to (1) assess and compare sedentary time (ST) of university students before and during the COVID-19 pandemic, (2) examine risk groups with regard to ST and the 'extent of change' in ST (from before to during the pandemic) in association with sociodemographic (gender, age), study-related (degree aspired to, field of study, semester), and pre-pandemic physical health-related [pre-pandemic physical activity (PA) and ST levels, pre-pandemic BMI class] variables, and (3) investigate whether the change in ST was predicted by these variables.!##!Methods!#!Two online surveys were conducted among students at the University of Mainz, Germany-the first in 2019 (before the pandemic) and the second in 2020 (during the pandemic). Participants of both surveys were included in a longitudinal sample. With the longitudinal sample's data, paired !##!Results!#!Of the !##!Conclusion!#!Even during a global pandemic lockdown, individuals who were previously more physically active and had less ST showed more health-promoting behavior in terms of ST. Therefore, it can be stated that efforts to promote PA and reduce ST are always valuable. Since ST increased and was worryingly high in all subgroups analyzed, all university students should be targeted by multidimensional approaches to tackle ST and promote their health