Dual transcriptomics to determine interferon-gamma independent host response to intestinal Cryptosporidium parvum infection

2021 ◽  
Author(s):  
Gina M. Gallego-Lopez ◽  
Carolina Mendoza Cavazos ◽  
Andrés M. Tibabuzo Perdomo ◽  
Andrew L. Garfoot ◽  
Roberta M. O’Connor ◽  
...  

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 IFNγ-KO mice. Murine intestinal sections were then sequenced to define the IFNγ 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 PBS or 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.

2017 ◽  
Vol 2017 ◽  
pp. 1-12 ◽  
Author(s):  
Bruno Hernáez ◽  
Graciela Alonso ◽  
Juan Manuel Alonso-Lobo ◽  
Alberto Rastrojo ◽  
Cornelius Fischer ◽  
...  

Vaccinia virus (VACV) encodes the soluble type I interferon (IFN) binding protein B18 that is secreted from infected cells and also attaches to the cell surface, as an immunomodulatory strategy to inhibit the host IFN response. By using next generation sequencing technologies, we performed a detailed RNA-seq study to dissect at the transcriptional level the modulation of the IFN based host response by VACV and B18. Transcriptome profiling of L929 cells after incubation with purified recombinant B18 protein showed that attachment of B18 to the cell surface does not trigger cell signalling leading to transcriptional activation. Consistent with its ability to bind type I IFN, B18 completely inhibited the IFN-mediated modulation of host gene expression. Addition of UV-inactivated virus particles to cell cultures altered the expression of a set of 53 cellular genes, including genes involved in innate immunity. Differential gene expression analyses of cells infected with replication competent VACV identified the activation of a broad range of host genes involved in multiple cellular pathways. Interestingly, we did not detect an IFN-mediated response among the transcriptional changes induced by VACV, even after the addition of IFN to cells infected with a mutant VACV lacking B18. This is consistent with additional viral mechanisms acting at different levels to block IFN responses during VACV infection.


Toxins ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 329
Author(s):  
Andrew Holmes ◽  
Jessie Sadlon ◽  
Keith Weaver

A majority of toxins produced by type I toxin–antitoxin (TA-1) systems are small membrane-localized proteins that were initially proposed to kill cells by forming non-specific pores in the cytoplasmic membrane. The examination of the effects of numerous TA-1 systems indicates that this is not the mechanism of action of many of these proteins. Enterococcus faecalis produces two toxins of the Fst/Ldr family, one encoded on pheromone-responsive conjugative plasmids (FstpAD1) and the other on the chromosome, FstEF0409. Previous results demonstrated that overexpression of the toxins produced a differential transcriptomic response in E. faecalis cells. In this report, we identify the specific amino acid differences between the two toxins responsible for the differential response of a gene highly induced by FstpAD1 but not FstEF0409. In addition, we demonstrate that a transporter protein that is genetically linked to the chromosomal version of the TA-1 system functions to limit the toxicity of the protein.


Cytokine ◽  
2012 ◽  
Vol 59 (3) ◽  
pp. 512
Author(s):  
Y. Wang ◽  
M. Swiecki ◽  
M. Cella ◽  
G. Alber ◽  
R.D. Schreiber ◽  
...  

2005 ◽  
Vol 19 (4) ◽  
pp. e12-e13
Author(s):  
Alicia Collado-Hidalgo ◽  
Caroline Y. Sung ◽  
Steve W. Cole

2008 ◽  
Vol 370 (2) ◽  
pp. 366-370 ◽  
Author(s):  
Shinya Kamitani ◽  
Norihiko Ohbayashi ◽  
Osamu Ikeda ◽  
Sumihito Togi ◽  
Ryuta Muromoto ◽  
...  

1986 ◽  
Vol 6 (12) ◽  
pp. 4770-4774 ◽  
Author(s):  
P Staeheli ◽  
P Danielson ◽  
O Haller ◽  
J G Sutcliffe

Mouse cells of the Mx+ genotype accumulate Mx mRNA in response to type I interferon (IFN). Nuclear runoff experiments show that IFN stringently regulates Mx gene expression at the level of transcription. Mx mRNA synthesis peaks about 3 h after IFN treatment, and within 5 h, Mx mRNA concentration rises from undetectable levels to about 0.1% of polyadenylated RNA.


2020 ◽  
Vol 34 (S1) ◽  
pp. 1-1 ◽  
Author(s):  
Andre Raymundo Borrego ◽  
Christian Corona-Ayala ◽  
Julienne Christa Salvador ◽  
Federico Christa Valdez ◽  
Manuel Llano

1998 ◽  
Vol 273 (5) ◽  
pp. 2714-2720 ◽  
Author(s):  
Susan L. Schafer ◽  
Rongtuan Lin ◽  
Paul A. Moore ◽  
John Hiscott ◽  
Paula M. Pitha

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