Inflammatory processes in a murine model of intra-abdominal abscess formation

Finlay‐Jones, John J.; Davies, Kate V. L.; Sturm, Lana; Kenny, Peter A.; Hart, Prue H.

doi:10.1002/jlb.66.4.583

Cited by 26 publications

(18 citation statements)

References 46 publications

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“…In human IAC, perforation or leakage of the GI tract is commonly associated with abscess formation but abscesses rarely result from infected peritoneal catheters. Sterile feces potentiates intra-abdominal infections by depleting complement-derived opsonins and impairing phagocytic killing (27,28). These effects likely account for our observation that tissue burdens and persistence of C. glabrata were increased in the presence of sterile feces, despite greater neutrophil counts.…”

Section: Ndmentioning

confidence: 68%

Candida glabrata Intra-Abdominal Candidiasis Is Characterized by Persistence within the Peritoneal Cavity and Abscesses

et al. 2014

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The pathogenesis of Candida glabrata infections is poorly understood. We studied the pathogenesis of intra-abdominal candidiasis (IAC) in mice that were infected intraperitoneally with C. glabrata and sterile feces. C. glabrata BG2 (5 ؋ 10 8 CFU) caused a 100% mortality rate. Sublethal inocula of BG2 (1 ؋ 10 8 or 1 ؋ 10 7 CFU) caused peritonitis that progressed to abscesses. Three clinical C. glabrata strains (5 ؋ 10 8 CFU) caused 80 to 100% mortality rates, while a fourth (strain 346) caused a 29% mortality rate. Following sublethal inocula (1 ؋ 10 7 CFU), the intra-abscess burdens of virulent strain 356 were ϳ1 log greater than those of strain 346. A C. glabrata ⌬plb1-2 mutant (phospholipase B genes disrupted) killed mice as well as BG2 did. When sublethal inocula were used, however, the ⌬plb1-2 mutant was associated with more rapid abscess resolution and lower intra-abscess burdens; these findings were reversed by PLB1 and PLB2 reinsertion. The ⌬plb1-2 mutant was also more susceptible than BG2 to killing by human neutrophils in vitro. BG2 and the ⌬plb1-2 mutant were indistinguishable during hematogenously disseminated candidiasis. C. albicans SC5314 was more virulent than C. glabrata BG2 during IAC, causing a 100% mortality rate following a challenge with 5 ؋ 10 7 CFU. In contrast, a sublethal inoculum (1 ؋ 10 7 CFU) of BG2 caused less neutrophil infiltration and greater burdens in peritoneal fluid than SC5314 did and abscesses that persisted longer and contained greater burdens. In conclusion, a mouse model of C. glabrata IAC mimics disease in humans and distinguishes the relative virulence of clinical and gene disruption strains. C. glabrata differed from C. albicans during IAC by being less lethal and eliciting dampened neutrophil responses but resulting in more persistent peritonitis and abscesses.

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Section: Ndmentioning

confidence: 68%

Candida glabrata Intra-Abdominal Candidiasis Is Characterized by Persistence within the Peritoneal Cavity and Abscesses

et al. 2014

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“…The recruitment of innate immune effector cells is important for the containment and control of bacterial infection, as well as abscess formation and localization (7). The characteristics of the adult response to sepsis have been well described but have not been fully delineated in the neonate (6,11,18).…”

Section: Resultsmentioning

confidence: 99%

Critical Role for CXC Ligand 10/CXC Receptor 3 Signaling in the Murine Neonatal Response to Sepsis

et al. 2011

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Previous studies have suggested that neonates rely heavily on innate immunity for their antimicrobial response to bacterial infections. However, the innate immune response by neonates to bacterial infection remains poorly characterized. Here, we show that in a murine model of neonatal polymicrobial sepsis, CXC ligand 10 (CXCL10) concentrations increase in the blood and peritoneum concordant with the peritoneal recruitment of granulocytes and macrophages. Additionally, CXC receptor 3 (CXCR3) expression on elicited peritoneal macrophages and granulocytes increases following sepsis. Blockade of CXCL10 worsens not only recruitment and phagocytic function of peritoneal granulocytes and macrophages but also survival. Deletion of CXCR3 also significantly increases mortality to a septic challenge. Finally, we demonstrate that the protective adjuvant effect of pretreatment with a Toll-like receptor 4 agonist to neonatal sepsis is dependent on an endogenous CXCL10 response and that pretreatment of neonates with CXCL10 can also significantly improve macrophage and granulocyte function and modestly improve outcome to polymicrobial sepsis. Together, these data suggest a critical role for CXCL10 signaling during neonatal sepsis.

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“…B. fragilis is the most common anaerobe isolated from intra-abdominal abscesses, and it has been demonstrated to possess many factors that promote its survival outside the intestinal tract, such as capsular polysaccharides, proteases, neuraminidase, iron acquisition, hemolysins, and resistance to oxidative stress (1,2,7,8). Oxidative stress occurs immediately when B. fragilis translocates from the anaerobic intestine to the more oxygenated (6% O 2 ) peritoneal cavity, and there is additional oxidative stress resulting from the immune response and polymorphonucleocyte (PMN) recruitment to the site of infection (9)(10)(11)(12). Thus, the oxidative stress response is needed for survival during abscess formation (13).…”

mentioning

confidence: 99%

Dps and DpsL Mediate SurvivalIn VitroandIn Vivoduring the Prolonged Oxidative Stress Response in Bacteroides fragilis

2015

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Bacteroides fragilis is a Gram-negative anaerobe and member of the human intestinal tract microbiome, where it plays many beneficial roles. However, translocation of the organism to the peritoneal cavity can lead to peritonitis, intra-abdominal abscess formation, bacteremia, and sepsis. During translocation, B. fragilis is exposed to increased oxidative stress from the oxygenated tissues of the peritoneal cavity and the immune response. In order to survive, B. fragilis mounts a robust oxidative stress response consisting of an acute and a prolonged oxidative stress (POST) response. This report demonstrates that the ability to induce high levels of resistance to tert-butyl hydroperoxide (tBOOH) after extended exposure to air can be linked to the POST response. Disk diffusion assays comparing the wild type to a ⌬dps mutant and a ⌬dps ⌬bfr mutant showed greater sensitivity of the mutants to tBOOH after exposure to air, suggesting that Dps and DpsL play a role in the resistance phenotype. Complementation studies with dps or bfr (encoding DpsL) restored tBOOH resistance, suggesting a role for both of these ferritin-family proteins in the response. Additionally, cultures treated with the iron chelator dipyridyl were not killed by tBOOH, indicating Dps and DpsL function by sequestering iron to prevent cellular damage. An in vivo animal model showed that the ⌬dps ⌬bfr mutant was attenuated, indicating that management of iron is important for survival within the abscess. Together, these data demonstrate a role for Dps and DpsL in the POST response which mediates survival in vitro and in vivo. IMPORTANCEB. fragilis is the anaerobe most frequently isolated from extraintestinal opportunistic infections, but there is a paucity of information about the factors that allow this organism to survive outside its normal intestinal environment. This report demonstrates that the iron storage proteins Dps and DpsL protect against oxidative stress and that they contribute to survival both in vitro and in vivo. Additionally, this work demonstrates an important role for the POST response in B. fragilis survival and provides insight into the complex regulation of this response. Bacteroides spp. are members of the normal intestinal microbiome of humans. The intestine is a consistent and favorable environment that provides continuous access to nutrient sources for these strictly anaerobic organisms. Bacteroides spp. play many important roles in maintaining a healthy intestinal tract, such as polysaccharide degradation, protection of the gut epithelia from colonization by pathogenic bacteria, development of the intestinal tract, maturation of the mucosal and systemic immune systems, and transformation of toxic and mutagenic compounds (1-4). However, when the integrity of the intestinal wall is breached due to trauma, abdominal surgery, or diseases such as appendicitis, perforated ulcer, diverticulitis, and colon cancer, translocation of the normal flora into the peritoneal cavity can result in peritonitis and establishment of an intr...

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Inflammatory processes in a murine model of intra-abdominal abscess formation

Cited by 26 publications

References 46 publications

Candida glabrata Intra-Abdominal Candidiasis Is Characterized by Persistence within the Peritoneal Cavity and Abscesses

Candida glabrata Intra-Abdominal Candidiasis Is Characterized by Persistence within the Peritoneal Cavity and Abscesses

Critical Role for CXC Ligand 10/CXC Receptor 3 Signaling in the Murine Neonatal Response to Sepsis

Dps and DpsL Mediate SurvivalIn VitroandIn Vivoduring the Prolonged Oxidative Stress Response in Bacteroides fragilis

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