Significance
The CD4
+
T
reg
response following acute
Listeria
infection is heterogeneous and deploys two distinct modes of suppression coinciding with initial pathogen exposure and resolution of infection. This bimodal suppression of CD8
+
T cells during priming and contraction is mediated by separate T
reg
lineages. These findings make a significant contribution to our understanding of the functional plasticity inherent within T
reg
s
, which allows these cells to serve as a sensitive and dynamic cellular rheostat for the immune system to prevent autoimmune pathology in the face of inflammation attendant to acute infection, enable expansion of the pathogen-specific response needed to control the infection, and reestablish immune homeostasis after the threat has been contained.
Throughout a 1-year period samples were obtained from 874 hogs at slaughter at one local, state-inspected slaughter plant. Caecal contents were the source of the samples. A total of 118 salmonellae was isolated yielding 16 different serovars. Major serovars were derby (57%), alachua (11%), agona (8%), and newport (5%). The average number of hogs sampled per trip was 17. The maximum number of serovars obtained at any one sampling day was 3. The maximum number of Salmonella-positive samples in any one day was 11 of 17 samples (64.7%). Total numbers of Salmonella isolates did not vary with season; however, during the hot, dry summer and fall seasons, 10 and 11 different serovars were isolated, respectively, compared to 3 and 1 serovars for the cooler, wetter winter and spring seasons, respectively.
Cross-presentation is a modular series of intracellular events dictating the internalization and subsequent MHC class I (MHC I) display of extracellular Ags. This process has been defined in dendritic cells and plays a fundamental role in the induction of CD8 T cell immunity during viral, intracellular bacterial, and antitumor responses. Herein, acute viral infection of murine liver with adenovirus, a model for intrahepatic cross-presentation, confirms hepatocytes directly contribute to cross-presentation of Ags and priming the pool of naive CD8 T cells within the liver microenvironment. Processing of soluble and cell-associated Ags into peptide displayed by MHC I is however defective in hepatocytes lacking collectrin, an intracellular chaperone protein that localizes within the endoplasmic reticulum-Golgi intermediate compartment. Loss of hepatic collectrin expression leads to the diminished cross-priming and expansion of cytolytic antiviral CD8 T cells. This study demonstrates that collectrin positively regulates processing of engulfed Ags into MHC I:peptide complexes within hepatocytes. Collectrin-mediated cross-presentation supports intrahepatic adaptive antiviral immune responses and may lead to insights into the nature of how the liver acts as a primary site of CD8 T cell activation.
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