Dual Transcriptomics To Determine Gamma Interferon- Independent Host Response to Intestinal Cryptosporidium parvum Infection

Gina M. Gallego-Lopez, Carolina Mendoza Cavazos, Andrés M. Tibabuzo Perdomo, Andrew L. Garfoot, Roberta M. O'Connor, Laura J. Knoll

Research output: Contribution to journalArticlepeer-review

Abstract

Animals with a chronic infection of the parasite Toxoplasma gondii are protected against lethal secondary infection with other pathogens. Our group previously determined that soluble T. gondii antigens (STAg) can mimic this protection and be used as a treatment against several lethal pathogens. Because treatments are limited for the parasite Cryptosporidium parvum, we tested STAg as a C. parvum therapeutic. We determined that STAg treatment reduced C. parvum Iowa II oocyst shedding in gamma interferon knockout (IFN-γ-KO) mice. Murine intestinal sections were then sequenced to define the IFN-γ-independent transcriptomic response to C. parvum infection. Gene Ontology and transcript abundance comparisons showed host immune response and metabolism changes. Transcripts for type I interferon-responsive genes were more abundant in C. parvum-infected mice treated with STAg. Comparisons between phosphate-buffered saline (PBS) and STAg treatments showed no significant differences in C. parvum gene expression. C. parvum transcript abundance was highest in the ileum and mucin-like glycoproteins and the GDP-fucose transporter were among the most abundant. These results will assist the field in determining both host- and parasite-directed future therapeutic targets.

Original languageEnglish (US)
Article numbere00638-21
JournalInfection and immunity
Volume90
Issue number2
DOIs
StatePublished - Feb 2022

Bibliographical note

Funding Information:
This work was funded by the National Institutes of Health (R21AI122898 RMO, L.J.K.; R01AI144016, L.J.K.; T32007215, C.M.C.), SciMed Graduate Research Scholars Fellowship UW—Madison (C.M.C.), Foster Wisconsin Distinguished Fellowship from the Food and Research Institute (C.M.C.), The Hartwell Foundation postdoctoral fellowship (A.L.G.), and a Morgridge postdoctoral fellowship supported by the Morgridge Institute for Research (G.M.G.-L.). The University of Wisconsin—Madison Flow Cytometry Core is supported by grant P30 CA014520. Funding bodies had no role in the design of the study and collection, analysis, and interpretation of data and in writing the manuscript.

Publisher Copyright:
© 2022 American Society for Microbiology. All rights reserved.

Keywords

  • Cecum
  • Cryptosporidium parvum
  • Ileum
  • RNA sequencing
  • STAg
  • Toxoplasma gondii
  • Interferon-gamma
  • Mice, Inbred C57BL
  • Transcriptome
  • Immunity
  • Cryptosporidium/genetics
  • Cryptosporidiosis
  • Animals
  • Mice

PubMed: MeSH publication types

  • Research Support, Non-U.S. Gov't
  • Journal Article
  • Research Support, N.I.H., Extramural

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