Modeling sepsis, with a special focus on large animal models of porcine peritonitis and bacteremia

Vintrych, Pavel; Al-Obeidallah, Mahmoud; Horák, Jan; Chvojka, J; Valešová, Lenka; Nalos, Lukáš; Jarkovská, Dagmar; Matějovič, Martin; Štengl, Milan

doi:10.3389/fphys.2022.1094199

Cited by 9 publications

(4 citation statements)

References 99 publications

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“…Currently, the diverse experimental models of peritonitis exist, and all of them have their advantages and disadvantages. The common models of peritonitis can be the methods of introduction of foreign bodies (Hryn et al, 2023a) or chemicals into the abdominal cavity, or bacterial contamination of the abdominal cavity with cultures of pathogenic microorganisms, or by opening the lumen of the colon or combination of both methods (Fantin et al, 2019;Montenegro et al, 2020;Vintrych et al, 2022). At the same time, thickening of the adipose tissue of the omentum, which, thereby, isolates the peritoneal cavity from the foci of inflammation was noted.…”

Section: Discussionmentioning

confidence: 99%

“…Experimental models of the peritonitis are crucial to obtain the reliable results. Currently, in experimental medicine, many different methods of modeling septic peritonitis are known (Sydorchuk, 2015;Vintrych et al, 2022;Brown et al, 2023). At the same time, in each case, the experiment should consider the optimal assessment of known etiological factors in its pathogenesis, among which the most common cases are ulcerative perforation of the stomach or duodenum, as well as perforation of the cecal appendage in its gangrenous inflammation (Hryn et al, 2022).…”

Section: Introductionmentioning

confidence: 99%

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Morphological Characteristics of the Results of Experimental Modeling of Septic Peritonitis

Hryn,

Maksymenko

2024

Int. J. Morphol.

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Experimental studies devoted to the study of the mechanisms of the pathogenesis of acute peritonitis and the development of new methods of medical and surgical treatment are becoming increasingly relevant. Today, experimental medicine knows many different ways to modeling septic peritonitis and eliminate it, but the role of the local immune system is underestimated, whereas it takes a direct part in inflammation. The objective of our work to study morphological features of results of experimental modeling of septic peritonitis in white rats. The study included 15 sexually mature white male rats weighing 276.75±6.56 grams. A simulation of septic peritonitis was performed by perforating the upper part of the cecum with four punctures with a G16 injection needle. As a result of the experiment, after examination of the peritoneal cavity, all 15 animals were diagnosed with omentum tamponade of perforated damage to the caecum. In 11 cases, the perforated wall of the caecum was covered by the greater omentum (73.34 %), and in the other 4 animals, tamponade was performed by one of the epididymal omentum (26.66 %). The initial stage of tamponade with the greater or epididymal omentums of a perforated caecum begins on the first day of the experiment and consists of tight interstitial consolidation between them, as well as in the invasion of blood vessels from the omentum side to the focus of infection, which ensure the delivery of the appropriate immunocompetent cells. As a result of this process, intensive lymphoid infiltrates are formed in this area, as well as the growth of adipose tissue, which isolates the inflammatory focus from the peritoneal cavity with a thick layer.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Morphological Characteristics of the Results of Experimental Modeling of Septic Peritonitis

Hryn,

Maksymenko

2024

Int. J. Morphol.

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“…In addition, the administration of C. albicans through intra-peritoneal injection in animal models does not replicate the complete spectrum of pathogenesis observed in human cases, including the interactions between the gut microbiota and the host before the breach of the intestinal barrier. Finally, the immune, inflammatory, and metabolic responses to infection in mice differ significantly from the human phenotype of sepsis [ 42 ].…”

Section: Discussionmentioning

confidence: 99%

Reappraisal of intra-abdominal candidiasis: insights from peritoneal fluid analysis

Novy,

Esposito,

Birckener

et al. 2023

ICMx

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Background The understanding of high mortality associated with intra-abdominal candidiasis (IAC) remains limited. While Candida is considered a harmless colonizer in the digestive tract, its role as a true pathogen in IAC is still debated. Evidence regarding Candida virulence in the human peritoneal fluid are lacking. We hypothesized that during IAC, Candida albicans develops virulence factors to survive to new environmental conditions. The objective of this observational exploratory monocentric study is to investigate the influence of peritoneal fluid (PF) on the expression of C. albicans virulence using a multimodal approach. Materials and methods A standardized inoculum of a C. albicans (3.106 UFC/mL) reference strain (SC5314) was introduced in vitro into various PF samples obtained from critically ill patients with intra-abdominal infection. Ascitic fluids (AFs) and Sabouraud medium (SBD) were used as control groups. Optical microscopy and conventional culture techniques were employed to assess the morphological changes and growth of C. albicans. Reverse transcriptase qPCR was utilized to quantify the expression levels of five virulence genes. The metabolic production of C. albicans was measured using the calScreener™ technology. Results A total of 26 PF samples from patients with secondary peritonitis were included in the study. Critically ill patients were mostly male (73%) with a median age of 58 years admitted for urgent surgery (78%). Peritonitis was mostly hospital-acquired (81%), including 13 post-operative peritonitis (50%). The infected PF samples predominantly exhibited polymicrobial composition. The findings revealed substantial variability in C. albicans growth and morphological changes in the PF compared to ascitic fluid. Virulence gene expression and metabolic production were dependent on the specific PF sample and the presence of bacterial coinfection. Conclusions This study provides evidence of C. albicans virulence expression in the peritoneal fluid. The observed variability in virulence expression suggests that it is influenced by the composition of PF and the presence of bacterial coinfection. These findings contribute to a better understanding of the complex dynamics of intra-abdominal candidiasis and advocate for personalized approach for IAC patients. Trial registrationhttps://clinicaltrials.gov/ (NCT05264571; February 22, 2022) Graphical Abstract

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“…Based on high similarities regarding size, physiology, reproductive cycles, immunology, and susceptibility to Ct, pigs have been used as biomedical animal models [9][10][11][12], including the study of immunity [13][14][15], STIs [16,17], and Ct vaccine development [18][19][20][21][22]. In addition, pigs can be infected both ocularly [23] and genitally [22,24] with C. suis (Cs).…”

Section: Introductionmentioning

confidence: 99%

A TriAdj-Adjuvanted Chlamydia trachomatis CPAF Protein Vaccine Is Highly Immunogenic in Pigs

Proctor,

Stadler,

Cortes

et al. 2024

Vaccines

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Chlamydia trachomatis (Ct) infections are the most common sexually transmitted infection (STI). Despite effective antibiotics for Ct, undetected infections or delayed treatment can lead to infertility, ectopic pregnancies, and chronic pelvic pain. Besides humans, chlamydia poses similar health challenges in animals such as C. suis (Cs) in pigs. Based on the similarities between humans and pigs, as well as their chlamydia species, we use pigs as a large biomedical animal model for chlamydia research. In this study, we used the pig model to develop a vaccine candidate against Ct. The vaccine candidate consists of TriAdj-adjuvanted chlamydial-protease-like activity factor (CPAF) protein. We tested two weekly administration options—twice intranasal (IN) followed by twice intramuscular (IM) and twice IM followed by twice IN. We assessed the humoral immune response in both serum using CPAF-specific IgG (including antibody avidity determination) and also in cervical and rectal swabs using CPAF-specific IgG and IgA ELISAs. The systemic T-cell response was analyzed following in vitro CPAF restimulation via IFN-γ and IL-17 ELISpots, as well as intracellular cytokine staining flow cytometry. Our data demonstrate that while the IN/IM vaccination mainly led to non-significant systemic immune responses, the vaccine candidate is highly immunogenic if administered IM/IN. This vaccination strategy induced high serum anti-CPAF IgG levels with strong avidity, as well as high IgA and IgG levels in vaginal and rectal swabs and in uterine horn flushes. In addition, this vaccination strategy prompted a pronounced cellular immune response. Besides inducing IL-17 production, the vaccine candidate induced a strong IFN-γ response with CD4 T cells. In IM/IN-vaccinated pigs, these cells also significantly downregulated their CCR7 expression, a sign of differentiation into peripheral-tissue-homing effector/memory cells. Conclusively, this study demonstrates the strong immunogenicity of the IM/IN-administered TriAdj-adjuvanted Ct CPAF vaccine candidate. Future studies will test the vaccine efficacy of this promising Ct vaccine candidate. In addition, this project demonstrates the suitability of the Cs pre-exposed outbred pig model for Ct vaccine development. Thereby, we aim to open the bottleneck of large animal models to facilitate the progression of Ct vaccine candidates into clinical trials.

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Modeling sepsis, with a special focus on large animal models of porcine peritonitis and bacteremia

Cited by 9 publications

References 99 publications

Morphological Characteristics of the Results of Experimental Modeling of Septic Peritonitis

Morphological Characteristics of the Results of Experimental Modeling of Septic Peritonitis

Reappraisal of intra-abdominal candidiasis: insights from peritoneal fluid analysis

A TriAdj-Adjuvanted Chlamydia trachomatis CPAF Protein Vaccine Is Highly Immunogenic in Pigs

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