scholarly journals Deciphering the landscape of host barriers to Listeria monocytogenes infection

2017 ◽  
Vol 114 (24) ◽  
pp. 6334-6339 ◽  
Author(s):  
Ting Zhang ◽  
Sören Abel ◽  
Pia Abel zur Wiesch ◽  
Jumpei Sasabe ◽  
Brigid M. Davis ◽  
...  
Keyword(s):  
Population Dynamics ◽  
Listeria Monocytogenes ◽  
Critical Role ◽  
Innate Immune ◽  
Microbial Populations ◽  
Multiple Organs ◽  
Founding Population ◽  
Food Borne ◽  
Listeria Monocytogenes Infection ◽  
The Impact

Listeria monocytogenes is a common food-borne pathogen that can disseminate from the intestine and infect multiple organs. Here, we used sequence tag-based analysis of microbial populations (STAMP) to investigate L. monocytogenes population dynamics during infection. We created a genetically barcoded library of murinized L. monocytogenes and then used deep sequencing to track the pathogen’s dissemination routes and quantify its founding population (Nb) sizes in different organs. We found that the pathogen disseminates from the gastrointestinal tract to distal sites through multiple independent routes and that Nb sizes vary greatly among tissues, indicative of diverse host barriers to infection. Unexpectedly, comparative analyses of sequence tags revealed that fecally excreted organisms are largely derived from the very small number of L. monocytogenes cells that colonize the gallbladder. Immune depletion studies suggest that distinct innate immune cells restrict the pathogen’s capacity to establish replicative niches in the spleen and liver. Finally, studies in germ-free mice suggest that the microbiota plays a critical role in the development of the splenic, but not the hepatic, barriers that prevent L. monocytogenes from seeding these organs. Collectively, these observations illustrate the potency of the STAMP approach to decipher the impact of host factors on population dynamics of pathogens during infection.

scholarly journals Aging predisposes to acute inflammatory induced pathology after tumor immunotherapy

2013 ◽  
Vol 210 (11) ◽  
pp. 2223-2237 ◽  
Author(s):  
Myriam N. Bouchlaka ◽  
Gail D. Sckisel ◽  
Mingyi Chen ◽  
Annie Mirsoian ◽  
Anthony E. Zamora ◽  
...  
Keyword(s):  
Critical Role ◽  
The Elderly ◽  
Mouse Tumor ◽  
Aged Mice ◽  
Liver Histopathology ◽  
Multiple Organs ◽  
The Impact ◽  
Young Mice

Cancer commonly occurs in the elderly and immunotherapy (IT) is being increasingly applied to this population. However, the majority of preclinical mouse tumor models assessing potential efficacy and toxicities of therapeutics use young mice. We assessed the impact of age on responses to systemic immune stimulation. In contrast to young mice, systemic cancer IT regimens or LPS given to aged mice resulted in rapid and lethal toxicities affecting multiple organs correlating with heightened proinflammatory cytokines systemically and within the parenchymal tissues. This inflammatory response and increased morbidity with age was independent of T cells or NK cells. However, prior in vivo depletion of macrophages in aged mice resulted in lesser cytokine levels, increased survival, and decreased liver histopathology. Furthermore, macrophages from aged mice and normal human elderly volunteers displayed heightened TNF and IL-6 production upon in vitro stimulation. Treatment of both TNF knockout mice and in vivo TNF blockade in aged mice resulted in significant increases in survival and lessened pathology. Importantly, TNF blockade in tumor-bearing, aged mice receiving IT displayed significant anti-tumor effects. These data demonstrate the critical role of macrophages in the age-associated hyper-inflammatory cytokine responses to systemic immunostimulation and underscore the importance of performing preclinical assessments in aged mice.

scholarly journals Muc2 mucin limits Listeria monocytogenes dissemination and modulates its population dynamics

2020 ◽  
Author(s):  
Ting Zhang ◽  
Jumpei Sasabe ◽  
Brandon Sit ◽  
Matthew K. Waldor
Keyword(s):  
Population Dynamics ◽  
Listeria Monocytogenes ◽  
Intestinal Tract ◽  
Systemic Disease ◽  
Major Constituent ◽  
Infection Model ◽  
Wild Type ◽  
Founding Population ◽  
Systemic Dissemination ◽  
Population Sizes

AbstractThe mucin Muc2 is a major constituent of the mucus layer that covers the intestinal epithelium and creates a barrier between epithelial cells and luminal commensal or pathogenic microorganisms. The Gram-positive food-borne pathogen Listeria monocytogenes can cause enteritis and also disseminate from the intestine to give rise to systemic disease. L. monocytogenes can bind to intestinal Muc2, but the influence of the Muc2 mucin barrier on L. monocytogenes intestinal colonization and systemic dissemination has not been explored. Here, we used an orogastric L. monocytogenes infection model to investigate the role of Muc2 in host defense against L. monocytogenes. Compared to wild-type mice, we found that Muc2-/- mice exhibited heightened susceptibility to orogastric challenge with L. monocytogenes, with higher mortality, elevated colonic pathology, and increased pathogen burdens in both the intestinal tract and distal organs. In contrast, L. monocytogenes burdens were equivalent in wild-type and Muc2-/- animals when the pathogen was administered intraperitoneally, suggesting that systemic immune defects do not explain the heightened pathogen dissemination observed with oral infection route. Using a barcoded L. monocytogenes library to measure intra-host pathogen population dynamics, we found that Muc2-/- animals had larger pathogen founding population sizes in the intestine and distal sites than observed in wild-type animals. Comparisons of barcode frequencies revealed that, in the absence of Muc2, the colon becomes the major source for seeding the internal organs. Together, our findings reveal that Muc2 limits L. monocytogenes dissemination from the intestinal tract and modulates its population dynamics during infection.

Lactoferricin influences early events of Listeria monocytogenes infection in THP-1 human macrophages

2004 ◽  
Vol 53 (2) ◽  
pp. 87-91 ◽  
Author(s):  
Catia Longhi ◽  
Maria P. Conte ◽  
Michela Penta ◽  
Alessia Cossu ◽  
Giovanni Antonini ◽  
...  
Keyword(s):  
Listeria Monocytogenes ◽  
Temperature Shift ◽  
Bactericidal Effect ◽  
Significant Inhibition ◽  
Host Cells ◽  
Bovine Lactoferrin ◽  
Antibacterial Effects ◽  
Food Borne ◽  
Listeria Monocytogenes Infection ◽  
Ifn Γ

Bovine lactoferrin (BLf) and its derivative peptide lactoferricin B (LfcinB) are known for their antimicrobial activity towards several pathogens, including Listeria monocytogenes, a food-borne Gram-positive invasive bacterium that infects a wide variety of host cells, including professional phagocytes. To add further information on the antibacterial effects of these compounds, the influence of BLf, LfcinB and the antimicrobial centre of LfcinB, the hexapeptide LfcinB4–9, on the invasive behaviour of L. monocytogenes was analysed in IFN-γ-activated human macrophagic cells (THP-1). Significant inhibition of bacterial entry in THP-1 cells was observed at LfcinB concentrations that were unable to produce any bacteriostatic or bactericidal effect, compared with BLf and LfcinB4–9 peptide. This inhibition occurred when LfcinB was incubated during the bacterial infection step and was not due only to competition for common glycosaminoglycan receptors. Assays performed through a temperature shift from 4 to 37 °C showed that inhibition of invasion took place at an early post-adsorption step, although an effect on a different step of intracellular infection could not be ruled out.

scholarly journals Increased Listeria monocytogenes Dissemination and Altered Population Dynamics in Muc2-Deficient Mice

2021 ◽  
Vol 89 (4) ◽  
Author(s):  
Ting Zhang ◽  
Jumpei Sasabe ◽  
Karthik Hullahalli ◽  
Brandon Sit ◽  
Matthew K. Waldor
Keyword(s):  
Population Dynamics ◽  
Listeria Monocytogenes ◽  
Systemic Disease ◽  
Foodborne Pathogen ◽  
Major Constituent ◽  
Infection Model ◽  
Wild Type ◽  
Content Type ◽  
Oral Infections ◽  
Founding Population

ABSTRACT The mucin Muc2 is a major constituent of the mucus layer that covers the intestinal epithelium and creates a barrier between epithelial cells and luminal commensal or pathogenic microorganisms. The Gram-positive foodborne pathogen Listeria monocytogenes can cause enteritis and also disseminate from the intestine to give rise to systemic disease. L. monocytogenes can bind to intestinal Muc2, but the influence of the Muc2 mucin barrier on L. monocytogenes intestinal colonization and systemic dissemination has not been explored. Here, we used an orogastric L. monocytogenes infection model to investigate the role of Muc2 in host defense against L. monocytogenes. Compared to wild-type mice, we found that Muc2−/− mice exhibited heightened susceptibility to orogastric challenge with L. monocytogenes, with higher mortality, elevated colonic pathology, and increased pathogen burdens in both the intestinal tract and distal organs. In contrast, L. monocytogenes burdens were equivalent in wild-type and Muc2−/− animals when the pathogen was administered intraperitoneally, suggesting that systemic immune defects related to Muc2 deficiency do not explain the heightened pathogen dissemination observed in oral infections. Using a barcoded L. monocytogenes library to measure intrahost pathogen population dynamics, we found that Muc2−/− animals had larger pathogen founding population sizes in the intestine and distal sites than observed in wild-type animals. Comparisons of barcode frequencies suggested that the colon becomes the major source for seeding the internal organs in Muc2−/− animals. Together, our findings reveal that Muc2 mucin plays a key role in controlling L. monocytogenes colonization, dissemination, and population dynamics.

scholarly journals Analyzing the innate immunity of NIH hairless mice and the impact of gut microbial polymorphisms on Listeria monocytogenes infection

Oncotarget ◽  
2017 ◽  
Vol 8 (63) ◽  
pp. 106222-106232 ◽  
Author(s):  
Zhong-Hao Ji ◽  
Wen-Zhi Ren ◽  
Wei Gao ◽  
Yang Hao ◽  
Wei Gao ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Listeria Monocytogenes ◽  
Hairless Mice ◽  
Listeria Monocytogenes Infection ◽  
The Impact

scholarly journals Immune Status and the Development of Listeria monocytogenes Infection in Aged and Young Guinea Pigs

2012 ◽  
Vol 35 (5) ◽  
pp. 309 ◽  
Author(s):  
Wen-Hsuan Wu ◽  
Hoan-Jen E. Pang ◽  
Karl R. Matthews
Keyword(s):  
Listeria Monocytogenes ◽  
Vitamin E ◽  
Foodborne Pathogen ◽  
The Elderly ◽  
Treated Group ◽  
Severe Illness ◽  
Microbiological Analysis ◽  
Control Groups ◽  
Listeria Monocytogenes Infection ◽  
The Impact

Purpose: Consuming even low numbers of the foodborne pathogen, Listeria monocytogenes, places the elderly at risk for severe illness. The impact of immunomodulation on the development of listerial infection within a young and aged population after low dose challenge with L. monocytogenes was investigated. Methods: Animals received daily supplementation of vitamin E for a period of 21 days to promote immunomodulation, and were then orally challenged with 100 CFU of L. monocytogenes. Levels of CD8+, CD4+ and CD3+ T cells were used as markers to determine the influence of daily supplementation with vitamin E on immune response; the spleen and liver were harvested for microbiological analysis. Results: Higher numbers of animals became infected in control groups than in vitamin E-treated group. During the post-challenge period, vitamin E-treated aged animals showed faster CD8+ T cell proliferation than control aged animals. Conclusion: Daily supplementation with vitamin E was more beneficial in young compared with aged animals in mitigating listerial infection. Results suggest exposure to even low numbers of L. monocytogenes can result in infection in both healthy young and aged populations.

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