Host factors in the resistance of newborn mice to K1 Escherichia coli infection

Pluschke, Gerd; Pelkonen, Sinikka

doi:10.1016/0882-4010(88)90051-4

Cited by 8 publications

(5 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To mimic E. coli or K. pneumoniae late onset neonatal sepsis, we inoculated neonatal mice (postnatal day 3-14) with either E. coli (10 4 CFU g −1 ) or K. pneumoniae (10 6 CFU g −1 ) respectively via intraperitoneal (i.p.) injection 15 and euthanized 72 h later or earlier if moribund. To asses bacterial burden we homogenized the spleen and liver in sterile PBS.…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

The microbiota regulates neutrophil homeostasis and host resistance to Escherichia coli K1 sepsis in neonatal mice

Deshmukh

Liu

Menkiti

et al. 2014

Nat Med

493

436

View full text Add to dashboard Cite

Acquisition of microbes by the neonate, which begins immediately during birth, is influenced by gestational age and mother’s microbiota and modified by exposure to antibiotics1. In neonates, prolonged duration of antibiotic therapy is associated with increased risk of sepsis after 4 days of life, known as late-onset sepsis (LOS)2, a disorder critically controlled by neutrophils3, but a role for the microbiota in regulating neutrophil behavior in the neonate has not been described. We exposed pregnant mouse dams to antibiotics in drinking water to limit transfer of maternal microbes to the neonates. Antibiotic exposure of dams decreased the total number of microbes in the intestine, altered the structure of intestinal microbiota and changed the pattern of microbial colonization. These changes were associated with decreased numbers of circulating and bone marrow neutrophils and granulocyte/macrophage restricted progenitor cells in the bone marrow. Antibiotic-exposure of dams attenuated the postnatal granulocytosis by reducing the number of interleukin (IL) 17-producing cells in intestine and consequent production of granulocyte colony stimulating factor (G-CSF). Relative granulocytopenia contributed to increased susceptibility of antibiotic-exposed neonatal mice to Escherichia coli K1 and Klebsiella pneumoniae sepsis, which could be partially reversed by administration of G-CSF. Restoration of normal microbiota, through TLR4- and MYD88-dependent mechanism, induced accumulation of IL17-producing type 3 innate lymphoid cells (ILC) in the intestine, promoted granulocytosis, and restored the IL17-dependent resistance to sepsis. Specific depletion of ILCs prevented the IL17- and G-CSF-dependent granulocytosis and resistance to sepsis. These data support a role for the intestinal microbiota in regulation of granulocytosis and host resistance to sepsis in the neonates.

show abstract

Section: Methodsmentioning

confidence: 99%

“…Neutrophils are essential in controlling infection due to E. coli serotype K1, an important cause of LOS and meningitis in human neonates 15 and the leading cause of death in preterm infants 16 . Neutropenia is an important risk factor in fatal neonatal sepsis 3 .…”

mentioning

confidence: 99%

The microbiota regulates neutrophil homeostasis and host resistance to Escherichia coli K1 sepsis in neonatal mice

Deshmukh

Liu

Menkiti

et al. 2014

Nat Med

493

436

View full text Add to dashboard Cite

show abstract

“…We grew S. pneumoniae serotype 19A (American Type Culture Collection 700674) or E. coli serotype K1 (82) or C. albicans (37°C, 200 rpm) in tryptic soy broth to log-phase growth. To mimic S. pneumoniae or E. coli or C. albicans pneumonia, we inoculated neonatal mice (P4 or P14) with either S. pneumoniae serotype 19A [10 5 colony-forming units (CFUs) g −1 ] or E. coli (10 4 CFU g −1 ) or C. albicans (10 5 CFU g −1 ), respectively, via intratracheal route.…”

Section: Murine Neonatal Pneumonia Studiesmentioning

confidence: 99%

Intestinal commensal bacteria mediate lung mucosal immunity and promote resistance of newborn mice to infection

et al. 2017

View full text Add to dashboard Cite

Immature mucosal defenses contribute to increased susceptibility of newborn infants to pathogens. Sparse knowledge of age-dependent changes in mucosal immunity has hampered improvements in neonatal morbidity due to infections. Here, we report that exposure of neonatal mice to commensal bacteria immediately after birth is required for a robust host defense against bacterial pneumonia, the leading cause of death in newborn infants. This crucial window was characterized by an abrupt influx of interleukin (IL)-22 producing group 3 innate lymphoid cells (IL22+ILC3) into the lungs of newborn mice. This influx was dependent on sensing of commensal bacteria by intestinal mucosal dendritic cells. Disruption of postnatal commensal colonization or selective depletion of dendritic cells interrupted the migratory program of lung IL-22+ILC3 and made the newborn mice more susceptible to pneumonia, which was reversed by transfer of commensal bacteria after birth. Thus, the resistance of newborn mice to pneumonia relied on commensal bacteria-directed ILC3-influx into the lungs, which mediated IL-22-dependent host resistance to pneumonia during this developmental window. These data establish that postnatal colonization by intestinal commensal bacteria is pivotal in the development of lung defenses in mice.

show abstract

“…E. coli K1-colonized neonatal rat pups, but not adult animals, subsequently develop lethal systemic infection, with E. coli K1 present in the blood circulation and brain tissue (15,19,20). Persistence of bacteria in the blood is dependent on the continued expression of the polySia capsule, as evidenced by the inability of capsule-defective mutants to cause systemic infection (21) and by the capacity of intraperitoneally delivered capsule-selective depolymerase to abrogate infection (16). Bacteria enter the CSF compartment of infected rat pups predominantly at the choroid plexus and penetrate superficial brain tissue (19), where they induce inflammation via proinflammatory cytokineinduced pathways involving interleukin-1␤ (IL-1␤), IL-6, and tumor necrosis factor ␣ (TNF-␣) (20).…”

mentioning

confidence: 99%

Altered Innate Defenses in the Neonatal Gastrointestinal Tract in Response to Colonization by Neuropathogenic Escherichia coli

et al. 2013

View full text Add to dashboard Cite

d Two-day-old (P2), but not 9-day-old (P9), rat pups are susceptible to systemic infection following gastrointestinal colonization by Escherichia coli K1. Age dependency reflects the capacity of colonizing K1 to translocate from gastrointestinal (GI) tract to blood. A complex GI microbiota developed by P2, showed little variation over P2 to P9, and did not prevent stable K1 colonization. Substantial developmental expression was observed over P2 to P9, including upregulation of genes encoding components of the small intestinal (␣-defensins Defa24 and Defa-rs1) and colonic (trefoil factor Tff2) mucus barrier. K1 colonization modulated expression of these peptides: developmental expression of Tff2 was dysregulated in P2 tissues and was accompanied by a decrease in mucin Muc2. Conversely, ␣-defensin genes were upregulated in P9 tissues. We propose that incomplete development of the mucus barrier during early neonatal life and the capacity of colonizing K1 to interfere with mucus barrier maturation provide opportunities for neuropathogen translocation into the bloodstream. The newborn infant is particularly vulnerable to systemic bacterial infection during the first 4 weeks of life, and mortality and morbidity associated with neonatal bacterial meningitis (NBM) and accompanying sepsis remain significant despite advances in antibacterial chemotherapy and supportive care (1, 2). In the developed world, Escherichia coli and group B streptococci are responsible for the majority of cases of NBM, and bacteria isolated from the cerebrospinal fluid of infected neonates invariably elaborate a protective polysaccharide capsule. Of neuroinvasive E. coli isolates, 80 to 85% express the K1 capsule (3, 4), a homopolymer of ␣-2,8-linked polysialic acid (polySia) that mimics the molecular structure of the polySia modulator of neuronal plasticity in mammalian hosts (5) and enables these strains to evade detection by a neonatal innate immune system undergoing a process of age-dependent maturation (6).Risk factors for NBM include obstetric and perinatal complications, premature birth, and low birth weight, particularly in low socioeconomic groups (7), but predisposition to infection is critically dependent on vertical transmission of the causative agent from mother to infant at or soon after birth (8). Although many aspects of the pathogenesis of E. coli K1 in NBM are unclear, maternally derived E. coli K1 bacteria are known to colonize the neonatal gastrointestinal (GI) tract (8, 9, 10), which is sterile at birth but rapidly acquires a complex microbiota that eventually converges toward a profile characteristic of the adult GI tract (11). E. coli K1 bacteria then translocate from the lumen of the small intestine or colon into the systemic circulation before entering the central nervous system (CNS) across the blood-brain barrier at the cerebral microvascular endothelium of the arachnoid membrane (12) or the blood-cerebrospinal fluid (CSF) barrier at the choroid plexus epithelium (13).Many of the temporal and spatial aspects of NBM can...

show abstract

Host factors in the resistance of newborn mice to K1 Escherichia coli infection

Cited by 8 publications

References 34 publications

The microbiota regulates neutrophil homeostasis and host resistance to Escherichia coli K1 sepsis in neonatal mice

The microbiota regulates neutrophil homeostasis and host resistance to Escherichia coli K1 sepsis in neonatal mice

Intestinal commensal bacteria mediate lung mucosal immunity and promote resistance of newborn mice to infection

Altered Innate Defenses in the Neonatal Gastrointestinal Tract in Response to Colonization by Neuropathogenic Escherichia coli

Contact Info

Product

Resources

About