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

doi:10.1128/iai.00638-21

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

Veterinary and Biomedical Sciences

Research output: Contribution to journal › Article › peer-review

6 Scopus citations

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 language	English (US)
Article number	e00638-21
Journal	Infection and immunity
Volume	90
Issue number	2
DOIs	https://doi.org/10.1128/iai.00638-21
State	Published - 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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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title = "Dual Transcriptomics To Determine Gamma Interferon- Independent Host Response to Intestinal Cryptosporidium parvum Infection",

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.",

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author = "Gallego-Lopez, {Gina M.} and Cavazos, {Carolina Mendoza} and {Tibabuzo Perdomo}, {Andr{\'e}s M.} and Garfoot, {Andrew L.} and O'Connor, {Roberta M.} and Knoll, {Laura J.}",

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: {\textcopyright} 2022 American Society for Microbiology. All rights reserved.",

year = "2022",

month = feb,

doi = "10.1128/iai.00638-21",

language = "English (US)",

volume = "90",

journal = "Infection and immunity",

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T1 - Dual Transcriptomics To Determine Gamma Interferon- Independent Host Response to Intestinal Cryptosporidium parvum Infection

AU - Gallego-Lopez, Gina M.

AU - Cavazos, Carolina Mendoza

AU - Tibabuzo Perdomo, Andrés M.

AU - Garfoot, Andrew L.

AU - O'Connor, Roberta M.

AU - Knoll, Laura J.

N1 - 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.

PY - 2022/2

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N2 - 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.

AB - 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.

KW - Cecum

KW - Cryptosporidium parvum

KW - Ileum

KW - RNA sequencing

KW - STAg

KW - Toxoplasma gondii

KW - Interferon-gamma

KW - Mice, Inbred C57BL

KW - Transcriptome

KW - Immunity

KW - Cryptosporidium/genetics

KW - Cryptosporidiosis

KW - Animals

KW - Mice

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DO - 10.1128/iai.00638-21

M3 - Article

C2 - 34928716

AN - SCOPUS:85124850466

SN - 0019-9567

VL - 90

JO - Infection and immunity

JF - Infection and immunity

IS - 2

M1 - e00638-21

ER -

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

Abstract

Bibliographical note

Keywords

PubMed: MeSH publication types

UN SDGs

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