Resistance to Yersinia pestis Infection Decreases with Age in B10.T(6R) Mice

Lambert, Nathaniel D.; Langfitt, Deanna; Nilles, Matthew L.; Bradley, David S.

doi:10.1128/iai.05267-11

Cited by 5 publications

(6 citation statements)

References 43 publications

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“…A recent study using fully virulent plague pathogens found that multiple loci were required for mice to survive in a Y. pestis subcutaneous infection model (32)(33)(34) (12), and DBA2/J mice (M. Tencati and R. Tapping, unpublished data). The resistance in BALB/cJ mice has been localized to chromosome 17, whereas at least part of the resistance in 129 mice localizes to chromosome 1.…”

Section: Discussionmentioning

confidence: 99%

“…We therefore chose to use inbred mice as a model to identify genes that may confer resistance against plague. We and others subsequently identified several inbred strains of mice that are resistant (11)(12)(13)(14). Resistance of the 129 line was first identified by Congleton et al in a pigmentation locus-negative (pgm Ϫ ) infection model of plague (11) but not for a fully virulent Y. pestis strain.…”

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confidence: 99%

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Resistance of Mice of the 129 Background to Yersinia pestis Maps to Multiple Loci on Chromosome 1

Tencati

Tapping

2016

Infect Immun

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Yersinia pestis is a Gram-negative bacterium that is the causative agent of bubonic and pneumonic plague. It is commonly acquired by mammals such as rodents and humans via the bite of an infected flea. We previously reported that multiple substrains of the 129 mouse background are resistant to pigmentation locus-negative (pgm ؊ ) Yersinia pestis and that this phenotype maps to a 30-centimorgan (cM) region located on chromosome 1. In this study, we have further delineated this plague resistance locus to a region of less than 20 cM through the creation and phenotyping of recombinant offspring arising from novel crossovers in this region. Furthermore, our experiments have revealed that there are at least two alleles in this initial locus, both of which are required for resistance on a susceptible C57BL/6 background. These two alleles work in trans since resistance is restored in offspring possessing one allele contributed by each parent. Our studies also indicated that the Slc11a1 gene (formerly known as Nramp1) located within the chromosome1 locus is not responsible for conferring resistance to 129 mice.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Resistance of Mice of the 129 Background to Yersinia pestis Maps to Multiple Loci on Chromosome 1

Tencati

Tapping

2016

Infect Immun

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“…Shin et al reported similar data using murine infection models of Clostridum difficile, and also hypothesized that this altered susceptibility to disease could be attributed, at least to some extent, to altered innate immunity associated with microbiota-dependent changes associated with age [81,82]. There have been several reports indicating a sex bias associated with Yersinia pestis susceptibility, with female mice being more resistant to infection [83][84][85]. Additionally, Lambert and coworkers demonstrated via several parameters that older mice are also more susceptible to plague disease compared to younger mice [84].…”

Section: Discussionmentioning

confidence: 82%

“…There have been several reports indicating a sex bias associated with Yersinia pestis susceptibility, with female mice being more resistant to infection [83][84][85]. Additionally, Lambert and coworkers demonstrated via several parameters that older mice are also more susceptible to plague disease compared to younger mice [84]. Using the Francisella live vaccine strain as a surrogate pathogen, Mares et al identified no significant differences associated with age and survival; they did, however, note several important differences that were impacted in aged mice, including polymorphonuclear neutrophil infiltration kinetics and cytokine expression levels [86].…”

Section: Discussionmentioning

confidence: 99%

The Impact of Age and Sex on Mouse Models of Melioidosis

et al. 2020

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Mouse models have been used to generate critical data for many infectious diseases. In the case of Burkholderia pseudomallei, mouse models have been invaluable for bacterial pathogenesis studies as well as for testing novel medical countermeasures including both vaccines and therapeutics. Mouse models of melioidosis have also provided a possible way forward to better understand the chronicity associated with this infection, as it appears that BALB/c mice develop an acute infection with B. pseudomallei, whereas the C57BL/6 model is potentially more suggestive of a chronic infection. Several unanswered questions, however, persist around this model. In particular, little attention has been paid to the effect of age or sex on the disease outcome in these animal models. In this report, we determined the LD 50 of the B. pseudomallei K96243 strain in both female and male BALB/c and C57BL/6 mice in three distinct age groups. Our data demonstrated a modest increase in susceptibility associated with sex in this model, and we documented important histopathological differences associated with the reproductive systems of each sex. There was a statistically significant inverse correlation between age and susceptibility. The older mice, in most cases, were more susceptible to the infection. Additionally, our retrospective analyses suggested that the impact of animal supplier on disease outcome in mice may be minimal. These observations were consistent regardless of whether the mice were injected with bacteria intraperitoneally or if they were exposed to aerosolized bacteria. All of these factors should be considered when designing experiments using mouse models of melioidosis.Pathogens 2020, 9, 113 2 of 18 has clearly demonstrated that it is quickly becoming a global concern [1-4]. B. pseudomallei can infect humans and animals via several routes of infection (i.e., inhalation of aerosolized bacteria, ingestion of contaminated drinking water, or through inoculation of a subcutaneous lesion) [5][6][7][8][9]. Inhalational melioidosis has been associated with monsoonal rains in endemic areas and is also a primary concern in the biodefense research community [10,11]. Pneumonia is a common presentation, which can be caused by a primary introduction of aerosolized bacteria into the lungs or a secondary pneumonia resulting from hematogenous spread to the lungs after a primary infection elsewhere [12,13]. There are currently no approved vaccines for B. pseudomallei and antibiotic treatment can be hampered by non-specific symptomology, the protracted two-phase course of treatment required, and the high rate of naturally occurring antibiotic-resistant strains [14,15]. Because of the public health and biodefense concerns associated with this bacterium, efforts are underway to develop effective medical countermeasures [15,16]. Accordingly, appropriate and well-characterized animal models are required for the development and testing of such efforts.The mouse model has afforded many research groups the opportunity to characterize the pathogen...

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“…Previous research from our laboratory has demonstrated differences in susceptibility of B10.T (6R) mice systemically infected with the KIM5 strain of Y. pestis. This difference was age dependent, where 2-month-old mice were more resistant than 5-to 12-month-old mice, with a difference in LD 50 of over 2 log (22).…”

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confidence: 98%

Difference in Strain Pathogenicity of Septicemic Yersinia pestis Infection in a TLR2 ^−/− Mouse Model

et al. 2020

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Yersinia pestis is the causative agent of bubonic, pneumonic, and septicemic plague. We demonstrate that Toll-like receptor 2-deficient (TLR2−/−) mice are resistant to septicemic infection by the KIM5 strain of Y. pestis but not to infection by the CO92 Δpgm strain. This resistance is dependent on TLR2, the route of infection, and the isoform of YopJ. Elevated bacterial burdens were found in the spleens of CO92 Δpgm-infected animals by 24 h postinfection and in the livers by 4 days. The YopJ isoform present contributed directly to cytotoxicity and inflammatory cytokine production of bone marrow-derived macrophages from TLR2−/− mice. Immune cell trafficking is altered in CO92 Δpgm infections, with an increased neutrophil infiltration to the spleen 5 days postinfection. Immune cell infiltration to the liver was greater and earlier in KIM5-infected TLR2−/− mice. The functionality of the immune cells was assessed by the ability to develop reactive oxygen and nitrogen species. Our data suggest an inhibition of granulocytes in forming these species in CO92 Δpgm-infected TLR2−/− mice. These findings suggest that resistance to KIM5 in TLR2−/− mice is dependent on early immune cell trafficking and functionality.

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Resistance to Yersinia pestis Infection Decreases with Age in B10.T(6R) Mice

Cited by 5 publications

References 43 publications

Resistance of Mice of the 129 Background to Yersinia pestis Maps to Multiple Loci on Chromosome 1

Resistance of Mice of the 129 Background to Yersinia pestis Maps to Multiple Loci on Chromosome 1

The Impact of Age and Sex on Mouse Models of Melioidosis

Difference in Strain Pathogenicity of Septicemic Yersinia pestis Infection in a TLR2 ^−/− Mouse Model

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Resistance to Yersinia pestis Infection Decreases with Age in B10.T(6R) Mice

Cited by 5 publications

References 43 publications

Resistance of Mice of the 129 Background to Yersinia pestis Maps to Multiple Loci on Chromosome 1

Resistance of Mice of the 129 Background to Yersinia pestis Maps to Multiple Loci on Chromosome 1

The Impact of Age and Sex on Mouse Models of Melioidosis

Difference in Strain Pathogenicity of Septicemic Yersinia pestis Infection in a TLR2 −/− Mouse Model

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Difference in Strain Pathogenicity of Septicemic Yersinia pestis Infection in a TLR2 ^−/− Mouse Model