Biology subjects

Cervantes, P. W.

Publications and source records attributed to Cervantes, P. W..

3 recordsLinked to original sources

bioRxiv2022

Sequence, Structure, and Epitope Analysis of the Polymorphic Membrane Protein Family in Chlamydia trachomatis

The polymorphic membrane proteins are a family of autotransporters that play an important role in infection, adhesion and immunity in Chlamydia trachomatis. Here we show that the characteristic GGA(I,L,V) and FxxN tetrapeptide repeats fit into a larger repeat sequence, and that these repeats correspond to the coils of a large beta-helical domain in high quality structure predictions. While the tetranucleotide motifs themselves are predicted to play a structural role in folding and close stacking of the beta-helical backbone of the passenger domain, we found many of the interesting features of Pmps are localized to the side loops jutting out from the beta helix - including protease cleavage, host cell adhesion, and B-cell epitopes; while T-cell epitopes are predominantly found in the beta-helix itself.

bioinformatics↗

bioRxiv2020

RIPK3 facilitates host and pathogen interactions after oral Toxoplasma gondii infection

Toxoplasma gondii infection activates pattern recognition receptor (PRR) pathways that drive innate inflammatory responses to control infection. Necroptosis is a pro-inflammatory cell death pathway apart of the innate immune response that has evolved to control pathogenic infection. In this study we further defined the role of Z-DNA binding protein 1 (ZBP1) as a PRR and assessed its contribution to necroptosis as a host protection mechanism to T. gondii infection. We found that ZBP1 does not induce pro-inflammatory necroptosis cell death and ZBP1 null mice have reduced survival after oral T. gondii infection. In contrast, mice deleted in receptor-interacting serine/threonine-protein kinase 3 (RIPK3-/-), a central mediator of necroptosis, have significantly improved survival after oral T. gondii infection even with higher parasite burden. The physiological consequences of RIPK3 activity did not show any differences in intestine villi immunopathology but RIPK3-/- mice showed higher immune cell infiltration and edema in the lamina propria. The contribution of necroptosis to host survival was clarified with mixed lineage kinase domain like pseudokinase null (MLKL-/-) mice. We found MLKL-/- mice to succumb to oral T. gondii infection the same as wild type mice, indicating necroptosis-independent RIPK3 activity impacts host survival. These results provide new insights on the impacts of pro-inflammatory cell death pathways as a mechanism of host defense to oral T. gondii infection.

microbiology↗

bioRxiv2019

Transcriptional analysis shows a robust host response to Toxoplasma gondii during early and late chronic infection in both male and female mice

The long-term host effects caused by the protozoan parasite Toxoplasma gondii are poorly understood. RNA-seq analysis previously determined that the host response in the brain was higher and more complex at 28 versus 10 days postinfection. Here, we analyzed the host transcriptional profile of age-and sex-matched mice during early (21 and 28 days) and late (3 and 6 months) chronic infection. We found that a majority of the host genes which increase in abundance at day 21 postinfection are still increased 6 months postinfection for both male and female mice. While most of the differentially expressed genes were similar between sexes, females have far fewer genes that are significantly less abundant, which may lead to the slight increased cyst burden in males. Transcripts for C-X-C Motif Chemokine Ligand 13 (CXCL13) and a C-C Motif Chemokine Receptor 2 (CCR2) were significantly higher in females compared to males during infection. As T. gondii chronic infection and profilin (PRF) confer resistance to Listeria monocytogenes infection in a CCR2 dependent manner, the sex specific difference in CCR2 expression lead us to re-test the protection of PRF in both sexes. Chronic infection as well as PRF were nearly as effective at reducing the bacterial burden in male versus female mice. These data show that most of the differentially express host genes are similar between males and females, important differences exist leading us to emphasize the inclusion of both sexes for future studies.

microbiology↗