Biology subjects

Donlan, A. N.

Publications and source records attributed to Donlan, A. N..

3 recordsLinked to original sources

bioRxiv2021

IL-13 promotes recovery from C. difficile infection

Clostridioides difficile infection (CDI) is the leading hospital-acquired infection in North America. We have previously discovered that antibiotic disruption of the gut microbiota decreases intestinal IL-33 and IL-25 and increases susceptibility to CDI. We further found that IL-33 promotes protection through type 2 Innate Lymphoid Cells (ILC2s), which produce IL-13. However, the contribution of IL-13 to disease has never been explored. We found that administration of IL-13 protected, and anti-IL-13 exacerbated CDI as measured by weight loss and clinical score, particularly during disease resolution. Additionally, concordant with IL-13 being important for M2 macrophage polarization, we saw a decrease in M2 macrophages (CD11B+CD64+CD206+) cells following neutralization of IL-13. We also observed monocyte accumulation as early as day three post-infection following IL-13 neutralization, suggesting IL-13 may be directly or indirectly important for their recruitment or transition into macrophages. Neutralization of the decoy receptor IL-13R2 resulted in protection from disease, likely through increased available endogenous IL-13. Our data highlight the protective role of IL-13 in promoting recovery from CDI and the association of poor responses with a dysregulated monocytemacrophage compartment. These results increase our understanding of type 2 immunity in CDI and may have implications for treating disease in patients.

immunology↗

bioRxiv2021

The IL-33-ILC2 pathway protects from amebic colitis

Entamoeba histolytica is a pathogenic protozoan parasite that causes intestinal colitis, diarrhea, and in some cases, liver abscess. Through transcriptomics analysis, we observed that E. histolytica infection was associated with increased expression of IL-33 mRNA in both the human and murine colon. IL-33, the IL-1 family cytokine, is released after cell injury to alert the immune system of tissue damage during infection. Treatment with recombinant IL-33 protected mice from amebic infection and colonic tissue damage; moreover, blocking IL-33 signaling made mice more susceptible to infection and weight loss. IL-33 limited the recruitment of inflammatory immune cells and decreased the pro-inflammatory cytokine IL-6 in the colon. Type 2 immune responses, which are known to be involved in tissue repair, were upregulated by IL-33 treatment during amebic infection. Interestingly, administration of IL-33 protected RAG2-/- mice but not RAG2-/-{gamma}c-/- mice, demonstrating that IL-33 mediated protection occurred in the absence of T or B cells but required the presence of innate lymphoid cells (ILCs). IL-33 induced recruitment of ILC2 but not ILC1 and ILC3 in RAG2-/- mice. Adoptive transfer of ILC2s to RAG2-/-{gamma}c-/- mice restored IL-33 mediated protection. These data reveal that the IL-33-ILC2 pathway is an important host defense mechanism against amebic colitis.

immunology↗

bioRxiv2020

Evaluation of K18-hACE2 mice as a model of SARS-CoV-2 infection

Abstract/SummaryMurine models of SARS-CoV-2 infection are critical for elucidating the biological pathways underlying COVID-19 disease. Because human ACE2 is the receptor for SARS-CoV-2, mice expressing the human ACE2 gene have shown promise as a potential model for COVID-19. Five mice from the transgenic mouse strain K18-hACE2 were intranasally inoculated with SARS-CoV-2 Hong Kong/VM20001061/2020. Mice were followed twice daily for five days and scored for weight loss and clinical symptoms. Infected mice did not exhibit any signs of infection until day four, when weight loss, but no other obvious clinical symptoms were observed. By day five all infected mice had lost around 10% of their original body weight, but exhibited variable clinical symptoms. All infected mice showed high viral titers in the lungs as well as altered lung histology associated with proteinaceous debris in the alveolar space, interstitial inflammatory cell infiltration and alveolar septal thickening. Overall, these results show that symptomatic SARS-CoV-2 infection can be established in the K18-hACE2 transgenic background and should be a useful mouse model for COVID-19 disease.

pathology↗