scholarly journals Hofbauer Cells Spread Listeria monocytogenes among Placental Cells and Undergo Pro-Inflammatory Reprogramming while Retaining Production of Tolerogenic Factors

mBio ◽  
2021 ◽  
Author(s):  
Siavash Azari ◽  
Lauren J. Johnson ◽  
Amy Webb ◽  
Sophia M. Kozlowski ◽  
Xiaoli Zhang ◽  
...  

Infection of the placental/fetal unit by the facultative intracellular pathogen Listeria monocytogenes results in severe pregnancy complications. Hofbauer cells (HBCs) are fetal macrophages that play homeostatic anti-inflammatory functions in healthy placentas.

Author(s):  
Monica R. Cesinger ◽  
Nicole H. Schwardt ◽  
Cortney R. Halsey ◽  
Maureen K. Thomason ◽  
Michelle L. Reniere

Listeria monocytogenes is a facultative intracellular pathogen and the causative agent of the foodborne illness listeriosis. L. monocytogenes must contend with reactive oxygen species generated extracellularly during aerobic growth and intracellularly by the host immune system. However, the mechanisms by which L. monocytogenes defends against peroxide toxicity have not yet been defined.


mBio ◽  
2019 ◽  
Vol 10 (5) ◽  
Author(s):  
Renate Frantz ◽  
Lisa Teubner ◽  
Tilman Schultze ◽  
Luigi La Pietra ◽  
Christin Müller ◽  
...  

ABSTRACT Cellular sensing of bacterial RNA is increasingly recognized as a determinant of host-pathogen interactions. The intracellular pathogen Listeria monocytogenes induces high levels of type I interferons (alpha/beta interferons [IFN-α/β]) to create a growth-permissive microenvironment during infection. We previously demonstrated that RNAs secreted by L. monocytogenes (comprising the secRNome) are potent inducers of IFN-β. We determined the composition and diversity of the members of the secRNome and found that they are uniquely enriched for noncoding small RNAs (sRNAs). Testing of individual sRNAs for their ability to induce IFN revealed several sRNAs with this property. We examined ril32, an intracellularly expressed sRNA that is highly conserved for the species L. monocytogenes and that was the most potent inducer of IFN-β expression of all the sRNAs tested in this study, in more detail. The rli32-induced IFN-β response is RIG-I (retinoic acid inducible gene I) dependent, and cells primed with rli32 inhibit influenza virus replication. We determined the rli32 motif required for IFN induction. rli32 overproduction promotes intracellular bacterial growth, and a mutant lacking rli32 is restricted for intracellular growth in macrophages. rli32-overproducing bacteria are resistant to H2O2 and exhibit both increased catalase activity and changes in the cell envelope. Comparative transcriptome sequencing (RNA-Seq) analysis indicated that ril32 regulates expression of the lhrC locus, previously shown to be involved in cell envelope stress. Inhibition of IFN-β signaling by ruxolitinib reduced rli32-dependent intracellular bacterial growth, indicating a link between induction of the interferon system and bacterial physiology. rli32 is, to the best of our knowledge, the first secreted individual bacterial sRNA known to trigger the induction of the type I IFN response. IMPORTANCE Interferons are potent and broadly acting cytokines that stimulate cellular responses to nucleic acids of unusual structures or locations. While protective when induced following viral infections, the induction of interferons is detrimental to the host during L. monocytogenes infection. Here, we identify specific sRNAs, secreted by the bacterium, with the capacity to induce type I IFN. Further analysis of the most potent sRNA, rli32, links the ability to induce RIG-I-dependent induction of the type I IFN response to the intracellular growth properties of the bacterium. Our findings emphasize the significance of released RNA for Listeria infection and shed light on a compartmental strategy used by an intracellular pathogen to modulate host responses to its advantage.


2015 ◽  
Vol 83 (8) ◽  
pp. 3146-3156 ◽  
Author(s):  
Grant S. Jones ◽  
Kate M. Bussell ◽  
Tanya Myers-Morales ◽  
Abigail M. Fieldhouse ◽  
Elsa N. Bou Ghanem ◽  
...  

Listeria monocytogenesis a highly adaptive bacterium that replicates as a free-living saprophyte in the environment as well as a facultative intracellular pathogen that causes invasive foodborne infections. The intracellular life cycle ofL. monocytogenesis considered to be its primary virulence determinant during mammalian infection; however, the proportion ofL. monocytogenesthat is intracellularin vivohas not been studied extensively. In this report, we demonstrate that the majority of wild-type (strain EGDe) and mouse-adapted (InlAm-expressing)L. monocytogenesrecovered from the mesenteric lymph nodes (MLN) was extracellular within the first few days after foodborne infection. In addition, significantly lower burdens ofL. monocytogeneswere recovered from the colon, spleen, and liver of gentamicin-treated mice than of control mice. This led us to investigate whether intracellular replication ofL. monocytogeneswas essential during the intestinal phase of infection. We found that lipoate protein ligase-deficientL. monocytogenes(ΔlplA1) mutants, which display impaired intracellular growth, were able to colonize the colon but did not persist efficiently and had a significant defect in spreading to the MLN, spleen, and liver. Together, these data indicate that the majority of theL. monocytogenesburden in the gastrointestinal tract is extracellular, but the small proportion of intracellularL. monocytogenesis essential for dissemination to the MLN and systemic organs.


mBio ◽  
2020 ◽  
Vol 11 (4) ◽  
Author(s):  
Bret N. Peterson ◽  
Megan K. M. Young ◽  
Shukun Luo ◽  
Jeffrey Wang ◽  
Aaron T. Whiteley ◽  
...  

ABSTRACT The facultative intracellular pathogen Listeria monocytogenes, like many related Firmicutes, uses the nucleotide second messenger cyclic di-AMP (c-di-AMP) to adapt to changes in nutrient availability, osmotic stress, and the presence of cell wall-acting antibiotics. In rich medium, c-di-AMP is essential; however, mutations in cbpB, the gene encoding c-di-AMP binding protein B, suppress essentiality. In this study, we identified that the reason for cbpB-dependent essentiality is through induction of the stringent response by RelA. RelA is a bifunctional RelA/SpoT homolog (RSH) that modulates levels of (p)ppGpp, a secondary messenger that orchestrates the stringent response through multiple allosteric interactions. We performed a forward genetic suppressor screen on bacteria lacking c-di-AMP to identify genomic mutations that rescued growth while cbpB was constitutively expressed and identified mutations in the synthetase domain of RelA. The synthetase domain of RelA was also identified as an interacting partner of CbpB in a yeast-2-hybrid screen. Biochemical analyses confirmed that free CbpB activates RelA while c-di-AMP inhibits its activation. We solved the crystal structure of CbpB bound and unbound to c-di-AMP and provide insight into the region important for c-di-AMP binding and RelA activation. The results of this study show that CbpB completes a homeostatic regulatory circuit between c-di-AMP and (p)ppGpp in Listeria monocytogenes. IMPORTANCE Bacteria must efficiently maintain homeostasis of essential molecules to survive in the environment. We found that the levels of c-di-AMP and (p)ppGpp, two nucleotide second messengers that are highly conserved throughout the microbial world, coexist in a homeostatic loop in the facultative intracellular pathogen Listeria monocytogenes. Here, we found that cyclic di-AMP binding protein B (CbpB) acts as a c-di-AMP sensor that promotes the synthesis of (p)ppGpp by binding to RelA when c-di-AMP levels are low. Addition of c-di-AMP prevented RelA activation by binding and sequestering CbpB. Previous studies showed that (p)ppGpp binds and inhibits c-di-AMP phosphodiesterases, resulting in an increase in c-di-AMP. This pathway is controlled via direct enzymatic regulation and indicates an additional mechanism of ribosome-independent stringent activation.


2011 ◽  
Vol 77 (18) ◽  
pp. 6559-6569 ◽  
Author(s):  
Edward M. Fox ◽  
Nola Leonard ◽  
Kieran Jordan

ABSTRACTThis study aimed to characterize physiological differences between persistent and presumed nonpersistentListeria monocytogenesstrains isolated at processing facilities and to investigate the molecular basis for this by transcriptomic sequencing. Full metabolic profiles of two strains, one persistent and one nonpersistent, were initially screened using Biolog's Phenotype MicroArray (PM) technology. Based on these results, in which major differences from selected antimicrobial agents were detected, another persistent strain and two nonpersistent strains were characterized using two antimicrobial PMs. Resistance to quaternary ammonium compounds (QACs) was shown to be higher among persistent strains. Growth of persistent and nonpersistent strains in various concentrations of the QACs benzethonium chloride (BZT) and cetylpyridinium chloride (CPC) was determined. Transcriptomic sequencing of a persistent and a presumed nonpersistent strain was performed to compare gene expression among these strains in the presence and absence of BZT. Two strains, designated “frequent persisters” because they were the most frequently isolated at the processing facility, showed overall higher resistance to QACs. Transcriptome analysis showed that BZT induced a complex peptidoglycan (PG) biosynthesis response, which may play a key role in BZT resistance. Comparison of persistent and nonpersistent strains indicated that transcription of many genes was upregulated among persistent strains. This included three gene operons:pdu,cob-cbi, andeut. These genes may play a role in the persistence ofL. monocytogenesoutside the human host.


2013 ◽  
Vol 79 (9) ◽  
pp. 2944-2951 ◽  
Author(s):  
Anne Holch ◽  
Kristen Webb ◽  
Oksana Lukjancenko ◽  
David Ussery ◽  
Benjamin M. Rosenthal ◽  
...  

ABSTRACTListeria monocytogenesis a food-borne human-pathogenic bacterium that can cause infections with a high mortality rate. It has a remarkable ability to persist in food processing facilities. Here we report the genome sequences for twoL. monocytogenesstrains (N53-1 and La111) that were isolated 6 years apart from two different Danish fish processers. Both strains are of serotype 1/2a and belong to a highly persistent DNA subtype (random amplified polymorphic DNA [RAPD] type 9). We demonstrate usingin silicoanalyses that both strains belong to the multilocus sequence typing (MLST) type ST121 that has been isolated as a persistent subtype in several European countries. The purpose of this study was to use genome analyses to identify genes or proteins that could contribute to persistence. In a genome comparison, the two persistent strains were extremely similar and collectively differed from the reference lineage II strain, EGD-e. Also, they differed markedly from a lineage I strain (F2365). On the proteome level, the two strains were almost identical, with a predicted protein homology of 99.94%, differing at only 2 proteins. No single-nucleotide polymorphism (SNP) differences were seen between the two strains; in contrast, N53-1 and La111 differed from the EGD-e reference strain by 3,942 and 3,471 SNPs, respectively. We included a persistentL. monocytogenesstrain from the United States (F6854) in our comparisons. Compared to nonpersistent strains, all three persistent strains were distinguished by two genome deletions: one, of 2,472 bp, typically contains the gene forinlF, and the other, of 3,017 bp, includes three genes potentially related to bacteriocin production and transport (lmo2774,lmo2775, and the 3′-terminal part oflmo2776). Further studies of highly persistent strains are required to determine if the absence of these genes promotes persistence. While the genome comparison did not point to a clear physiological explanation of the persistent phenotype, the remarkable similarity between the two strains indicates that subtypes with specific traits are selected for in the food processing environment and that particular genetic and physiological factors are responsible for the persistent phenotype.


2015 ◽  
Vol 83 (8) ◽  
pp. 3233-3242 ◽  
Author(s):  
Lena Meyer ◽  
Jeanette E. Bröms ◽  
Xijia Liu ◽  
Martin E. Rottenberg ◽  
Anders Sjöstedt

Certain intracellular bacteria use the host cell cytosol as the replicative niche. Although it has been hypothesized that the successful exploitation of this compartment requires a unique metabolic adaptation, supportive evidence is lacking. ForFrancisella tularensis, many genes of theFrancisellapathogenicity island (FPI) are essential for intracellular growth, and therefore, FPI mutants are useful tools for understanding the prerequisites of intracytosolic replication. We compared the growth of bacteria taken up by phagocytic or nonphagocytic cells with that of bacteria microinjected directly into the host cytosol, using the live vaccine strain (LVS) ofF. tularensis; five selected FPI mutants thereof, i.e., ΔiglA, ΔiglÇ ΔiglG, ΔiglI, and ΔpdpEstrains; andListeria monocytogenes. After uptake in bone marrow-derived macrophages (BMDM), ASC−/−BMDM, MyD88−/−BMDM, J774 cells, or HeLa cells, LVS, ΔpdpEand ΔiglGmutants, andL. monocytogenesreplicated efficiently in all five cell types, whereas the ΔiglAand ΔiglCmutants showed no replication. After microinjection, all 7 strains showed effective replication in J774 macrophages, ASC−/−BMDM, and HeLa cells. In contrast to the rapid replication in other cell types,L. monocytogenesshowed no replication in MyD88−/−BMDM and LVS showed no replication in either BMDM or MyD88−/−BMDM after microinjection. Our data suggest that the mechanisms of bacterial uptake as well as the permissiveness of the cytosolic compartmentper seare important factors for the intracytosolic replication. Notably, none of the investigated FPI proteins was found to be essential for intracytosolic replication after microinjection.


2005 ◽  
Vol 6 (2) ◽  
pp. 211-217 ◽  
Author(s):  
Charles J. Czuprynski

AbstractListeria monocytogenesis amongst the most intriguing and well studied of the pathogenic bacteria. However, the understanding and perspective one has ofL. monocytogenesdepends to a large extent on the microbiological issues with which one is faced as a part of your professional duties. The focus of the veterinary clinician or investigator is likely to be foremost on the neurologic (circling disease) and reproductive diseasesL. monocytogenescauses. To the food microbiologist, the principal concern is to prevent introduction ofL. monocytogenesinto food products, or to identify its presence and prevent its multiplication to numbers of organisms that are likely to pose a substantial risk to humans who ingest the product. To the cellular immunologist, listeriosis represents a robust murine model that helped to elucidate many important concepts in innate and adaptive immunity, andL. monocytogenesis a potential vector for delivery of novel vaccines. To the student of molecular pathogenesis,L. monocytogenesis a powerful and well-characterized model organism for studying the cellular microbiology of an intracellular pathogen. In this brief overview, I will attempt to highlight some of the classical observations, and contemporary insights, onL. monocytogenesand listeriosis, and integrate these perspectives into a common framework. By so doing, I hope to provide those with one perspective on listeriosis with an appreciation of the broad array of problems and issues faced by those who focus on some other aspect ofL. monocytogenesand its pathogenesis.


2018 ◽  
Vol 6 (25) ◽  
Author(s):  
Thao D. Tran ◽  
Steven Huynh ◽  
Craig T. Parker ◽  
Robert Hnasko ◽  
Lisa Gorski ◽  
...  

ABSTRACT Here, we report the complete genome sequences of three Bacillus amyloliquefaciens strains isolated from alfalfa, almond drupes, and grapes that inhibited the growth of Listeria monocytogenes strain 2011L-2857 in vitro. We also report multiple gene clusters encoding secondary metabolites that may be responsible for the growth inhibition of L. monocytogenes.


2018 ◽  
Vol 7 (13) ◽  
Author(s):  
Yanhong Liu ◽  
Aixia Xu ◽  
Pina M. Fratamico ◽  
Christopher H. Sommers ◽  
Luca Rotundo ◽  
...  

Listeria monocytogenes is an important foodborne pathogen that causes listeriosis. Here, we report the draft genome sequences of seven L. monocytogenes strains isolated from food, environmental, and clinical sources.


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