Rat strain differences in peritoneal immune cell response to selected gut microbiota: A crossroad between tolerance and autoimmunity?

Veljko Blagojević, Vesna Kovačević-Jovanović, Ivana Ćuruvija, Raisa Petrović, Ivana Vujnović, Vesna Vujić, Stanislava Stanojević

Some gut commensals can be protective, whereas others are implicated as necessary for development of inflammatory/autoimmune diseases. Peritoneal immune cells may play an important role in promoting autoimmunity in response to gut microbiota. This study investigated the phenotype and the function of peritoneal immune cells in the autoimmunity-resistant Albino Oxford (AO), and the autoimmunity-prone Dark Agouti (DA) rat strains upon stimulation with their own colonic E. coli or Enterococcus. Rats were intraperitoneally injected with their own E. coli or Enterococcus. Peritoneal cells isolated two days later were tested for nitric oxide (NO) and cytokine production, and for arginase and myeloperoxidase (MPO) activity. The phenotype of cells was determined using flow cytometry. While the Enterococcus injection did not affect the composition of peritoneal cells in AO rats, the E. coli treatment increased the percentages of activated CD11bintHIS48hi neutrophils, and decreased the proportion of resident (CD11bhiHIS48int/low, CD163 + CD86+) and anti-inflammatory CD68 + CD206+ macrophages. E. coli increased the production of NO and urea, but preserved their ratio in cells from AO rats. Conversely, both E. coli and Enterococcus diminished the proportion of resident and anti-inflammatory macrophages, increased the proportion of activated neutrophils, and induced inflammatory polarization of peritoneal cells in DA rats. However, injection of E. coli maintained the ratio of typical CD11bintHIS48int neutrophils in DA rats, which correlated with the sustained MPO activity. The rat strain differences in peritoneal cell response to own commensal microbiota may contribute to differential susceptibility to inflammatory/autoimmune diseases.