scholarly journals Role of Genetic Resistance in Invasive Pneumococcal Infection: Identification and Study of Susceptibility and Resistance in Inbred Mouse Strains

2001 ◽  
Vol 69 (1) ◽  
pp. 426-434 ◽  
Author(s):  
Neill A. Gingles ◽  
Janet E. Alexander ◽  
Aras Kadioglu ◽  
Peter W. Andrew ◽  
Alison Kerr ◽  
...  
Keyword(s):  
Inbred Mice ◽  
Inbred Mouse ◽  
Genetic Resistance ◽  
Pneumococcal Infection ◽  
Mouse Strains ◽  
Inflammatory Lesions ◽  
Invasive Pneumococcal Infection ◽  
Susceptibility And Resistance

ABSTRACT From a panel of nine inbred mice strains intranasally infected withStreptococcus pneumoniae type 2 strain, BALB/c mice were resistant and CBA/Ca and SJL mice were susceptible to infection. Further investigation revealed that BALB/c mice were able to prevent proliferation of pneumococci in the lungs and blood, whereas CBA/Ca mice showed no bacterial clearance. Rapidly increasing numbers of bacteria in the blood was a feature of CBA/Ca but not BALB/c mice. In the lungs, BALB/c mice recruited significantly more neutrophils than CBA/Ca mice at 12 and 24 h postinfection. Inflammatory lesions in BALB/c mice were visible much earlier than in CBA/Ca mice, and there was a greater cellular infiltration into the lung tissue of BALB/c mice at the earlier time points. Our data suggest that resistance or susceptibility to intranasal pneumococci may have an association with recruitment and/or function of neutrophils.

scholarly journals Role of CD4+ and CD8+ T cells in the prevention of measles virus-induced encephalitis in mice

2000 ◽  
Vol 81 (11) ◽  
pp. 2707-2713 ◽  
Author(s):  
Gerald Weidinger ◽  
Stefanie Czub ◽  
Claudia Neumeister ◽  
Pat Harriott ◽  
Volker ter Meulen ◽  
...  
Keyword(s):  
T Cells ◽  
Measles Virus ◽  
Inbred Mouse ◽  
Cell Epitope ◽  
Mouse Strains ◽  
Protective Capacity ◽  
Mhc Haplotype ◽  
Susceptibility And Resistance

Depending on their major histocompatibility complex (MHC) haplotype, inbred mouse strains are either resistant (H2-d, BALB/c), susceptible (H2-k, C3H) or partially resistant (H2-d×k, BaCF1) to intracerebral infection with the neurotropic rodent-adapted measles virus (MV) strain CAM/RBH. Here, mortality is demonstrated to be correlated directly with virus spread and virus replication in the CNS and to be inversely correlated with the activation of MV-specific T cells. Previously, it has been shown that primary CD4+ T cells alone are protective in the resistant background. In the susceptible background, CD4+ T cells acquire protective capacity after immunization with a newly defined CD4+ T cell epitope peptide. In the partially resistant mice, CD4+ T cells provide help for CD8+ T cells and protect in cooperation with them. It seems that the lytic capacity of CD8+ T cells is crucial in providing protection, as MV-specific Ld-restricted CD8+ T cells, which are highly lytic in vitro after transfer, protect naive animals against MV-induced encephalitis (MVE). In contrast, Kk-restricted CD8+ T cells with low lytic capacity do not protect. In the MVE model, CD4+ T cells are able to protect either alone (resistant mice), through cooperation with CD8+ T cells (intermediate susceptible) or after immunization as secondary T cells (susceptible mice). CD8+ T cells are able to protect alone after immunization if they are cytolytic. Thus, susceptibility and resistance depend upon the functional composition of CD4+ and CD8+ T cells governed by the MHC haplotype.

scholarly journals Role of Inflammatory Mediators in Resistance and Susceptibility to Pneumococcal Infection

2002 ◽  
Vol 70 (3) ◽  
pp. 1547-1557 ◽  
Author(s):  
Alison R. Kerr ◽  
June J. Irvine ◽  
Jennifer J. Search ◽  
Neill A. Gingles ◽  
Aras Kadioglu ◽  
...  
Keyword(s):  
Core Body Temperature ◽  
Inbred Mouse ◽  
Pneumococcal Infection ◽  
Mouse Strains ◽  
Isolated Lung ◽  
Cytokine Tumor Necrosis Factor ◽  
Core Body ◽  
Necrosis Factor

ABSTRACT Variations in the host response during pneumonia caused by Streptococcus pneumoniae in susceptible (CBA/Ca) and resistant (BALB/c) inbred mouse strains were investigated. Significant differences were detected in survival time, core body temperature, lung-associated and systemic bacterial loads, mast cell numbers, magnitude and location of cytokine production, lung disruption, and ability of isolated lung cells to release the cytokine tumor necrosis factor (TNF) alpha in vitro. Overall, the results indicate that the reduced capacity of CBA/Ca mice to induce rapid TNF activity within the airways following infection with S. pneumoniae may be a factor in their elevated susceptibility to pneumococcal pneumonia.

scholarly journals Terc Gene Cluster Variants Predict Liver Telomere Length in Mice

Cells ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 2623
Author(s):  
Dana Zeid ◽  
Sean Mooney-Leber ◽  
Laurel R. Seemiller ◽  
Lisa R. Goldberg ◽  
Thomas J. Gould
Keyword(s):  
Linkage Disequilibrium ◽  
Telomere Length ◽  
Gene Cluster ◽  
Inbred Mice ◽  
Inbred Mouse ◽  
Mouse Strains ◽  
Chromosome 3 ◽  
Human Populations ◽  
Nucleotide Polymorphisms ◽  
Initial Finding

Variants in a gene cluster upstream-adjacent to TERC on human chromosome 3, which includes genes APRM, LRRC31, LRRC34 and MYNN, have been associated with telomere length in several human populations. Currently, the mechanism by which variants in the TERC gene cluster influence telomere length in humans is unknown. Given the proximity between the TERC gene cluster and TERC (~0.05 Mb) in humans, it is speculated that cluster variants are in linkage disequilibrium with a TERC causal variant. In mice, the Terc gene/Terc gene cluster are also located on chromosome 3; however, the Terc gene cluster is located distantly downstream of Terc (~60 Mb). Here, we initially aim to investigate the interactions between genotype and nicotine exposure on absolute liver telomere length (aTL) in a panel of eight inbred mouse strains. Although we found no significant impact of nicotine on liver aTL, this first experiment identified candidate single nucleotide polymorphisms (SNPs) in the murine Terc gene cluster (within genes Lrrc31, Lrriq4 and Mynn) co-varying with aTL in our panel. In a second experiment, we tested the association of these Terc gene cluster variants with liver aTL in an independent panel of eight inbred mice selected based on candidate SNP genotype. This supported our initial finding that Terc gene cluster polymorphisms impact aTL in mice, consistent with data in human populations. This provides support for mice as a model for telomere dynamics, especially for studying mechanisms underlying the association between Terc cluster variants and telomere length. Finally, these data suggest that mechanisms independent of linkage disequilibrium between the Terc/TERC gene cluster and the Terc/TERC gene mediate the cluster’s regulation of telomere length.

scholarly journals Mouse Susceptibility to Anthrax Lethal Toxin Is Influenced by Genetic Factors in Addition to Those Controlling Macrophage Sensitivity

2004 ◽  
Vol 72 (8) ◽  
pp. 4439-4447 ◽  
Author(s):  
Mahtab Moayeri ◽  
Nathaniel W. Martinez ◽  
Jason Wiggins ◽  
Howard A. Young ◽  
Stephen H. Leppla
Keyword(s):  
Genetic Factors ◽  
Inbred Mouse ◽  
Inbred Strains ◽  
Lethal Toxin ◽  
Cytokine Response ◽  
Mouse Strains ◽  
Anthrax Lethal Toxin ◽  
Toll Like Receptor 4 ◽  
Oxide Synthase

ABSTRACT Bacillus anthracis lethal toxin (LT) produces symptoms of anthrax in mice and induces rapid lysis of macrophages (Mφ) derived from certain inbred strains. We used nine inbred strains and two inducible nitric oxide synthase (iNOS) knockout C57BL/6J strains polymorphic for the LT Mφ sensitivity Kif1C locus to analyze the role of Mφ sensitivity (to lysis) in LT-mediated cytokine responses and lethality. LT-mediated induction of cytokines KC, MCP-1/JE, MIP-2, eotaxin, and interleukin-1β occurred only in mice having LT-sensitive Mφ. However, while iNOS knockout C57BL/6J mice having LT-sensitive Mφ were much more susceptible to LT than the knockout mice with LT-resistant Mφ, a comparison of susceptibilities to LT in the larger set of inbred mouse strains showed a lack of correlation between Mφ sensitivity and animal susceptibility to toxin. For example, C3H/HeJ mice, harboring LT-sensitive Mφ and having the associated LT-mediated cytokine response, were more resistant than mice with LT-resistant Mφ and no cytokine burst. Toll-like receptor 4 (Tlr4)-deficient, lipopolysaccharide-nonresponsive mice were not more resistant to LT. We also found that CAST/Ei mice are uniquely sensitive to LT and may provide an economical bioassay for toxin-directed therapeutics. The data indicate that while the cytokine response to LT in mice requires Mφ lysis and while Mφ sensitivity in the C57BL/6J background is sufficient for BALB/cJ-like mortality of that strain, the contribution of Mφ sensitivity and cytokine response to animal susceptibility to LT differs among other inbred strains. Thus, LT-mediated lethality in mice is influenced by genetic factors in addition to those controlling Mφ lysis and cytokine response and is independent of Tlr4 function.

scholarly journals Genetic Resistance of Mice to Mycobacterium paratuberculosis Is Influenced by Slc11a1 at the Early but Not at the Late Stage of Infection

2008 ◽  
Vol 76 (5) ◽  
pp. 2099-2105 ◽  
Author(s):  
Virginie Roupie ◽  
Valérie Rosseels ◽  
Virginie Piersoel ◽  
Denise K. Zinniel ◽  
Raúl G. Barletta ◽  
...  
Keyword(s):  
Vibrio Harveyi ◽  
Inbred Mouse ◽  
Genetic Resistance ◽  
Mouse Strains ◽  
Inbred Mouse Strains ◽  
Mycobacterium Paratuberculosis ◽  
Susceptible Mouse ◽  
Resistance To Infection ◽  
Bacterial Replication ◽  
Interferon Responses

ABSTRACT We have recently described the development of a luminescent Mycobacterium paratuberculosis strain of bovine origin expressing the luxAB genes of Vibrio harveyi. With this luminescent isolate, fastidious and costly enumeration of CFU by plating them on agar can be replaced by easy and rapid luminometry. Here, we have reevaluated the effect of Slc11a1 (formerly Nramp1) polymorphism on susceptibility to M. paratuberculosis, using this luminometric method. A series of inbred mouse strains were infected intravenously with luminescent M. paratuberculosis S-23 and monitored for bacterial replication in spleen, liver, and lungs for 12 weeks. The results indicate that, as for Mycobacterium avium subsp. avium, innate resistance to infection is genetically controlled by Slc11a1. In BALB/c, congenic BALB.B10-H2b (BALB/c background; H-2 b ), C57BL/6, and beige C57BL/6 bg/ bg mice (all Slc11a1 s ), bacterial numbers in spleen and liver remained unchanged during the first 4 weeks of infection, whereas in DBA/2 and congenic BALB/c.DBA/2 (C.D2) mice (both Slc11a1 r ) and in (C57BL/6 × DBA/2)F1 mice (Slc11a1 s/r ), the bacterial numbers had decreased more than 10-fold at 4 weeks postinfection in both male and female mice. At later time points, additional differences in bacterial replication were observed between the susceptible mouse strains, particularly in the liver. Whereas bacterial numbers in the liver gradually decreased more than 100-fold in C57BL/6 mice between week 4 and week 12, bacterial numbers were stable in livers from BALB/c and beige C57BL/6 bg/ bg mice during this period. Mycobacterium-specific gamma interferon responses developed earlier and to a higher magnitude in C57BL/6 mice than in BALB/c mice and were lowest in resistant C.D2 mice.

scholarly journals Structural and functional studies of the early T lymphocyte activation 1 (Eta-1) gene. Definition of a novel T cell-dependent response associated with genetic resistance to bacterial infection.

1989 ◽  
Vol 170 (1) ◽  
pp. 145-161 ◽  
Author(s):  
R Patarca ◽  
G J Freeman ◽  
R P Singh ◽  
F Y Wei ◽  
T Durfee ◽  
...  
Keyword(s):  
T Cell ◽  
Bacterial Infection ◽  
T Lymphocyte ◽  
Inbred Mouse ◽  
Genetic Resistance ◽  
Lymphocyte Activation ◽  
Cellular Adhesion ◽  
Mouse Strains ◽  
T Lymphocyte Activation

We describe a murine cDNA, designated Early T lymphocyte activation 1 (ETA-1) which is abundantly expressed after activation of T cells. Eta-1 encodes a highly acidic secreted product having structural features of proteins that bind to cellular adhesion receptors. The Eta-1 gene maps to a locus on murine chromosome 5 termed Ric that confers resistance to infection by Rickettsia tsutsugamushi (RT), an obligate intracellular bacterium that is the etiological agent for human scrub typhus. With one exception, inbred mouse strains that expressed the Eta-1a allele were resistant to RT infection (RicR), and inbred strains expressing the Eta-1b allele were susceptible (RicS). These findings suggest that Eta-1 is the gene inferred from previous studies of the Ric locus (5). Genetic resistance to RT infection is associated with a strong Eta-1 response in vivo and inhibition of early bacterial replication. Eta-1 gene expression appears to be part of a surprisingly rapid T cell-dependent response to bacterial infection that may precede classical forms of T cell-dependent immunity.

scholarly journals Susceptibility and resistance to poliovirus-induced paralysis of inbred mouse strains.

1991 ◽  
Vol 65 (2) ◽  
pp. 1035-1040 ◽  
Author(s):  
B Jubelt ◽  
S L Ropka ◽  
S Goldfarb ◽  
C Waltenbaugh ◽  
R P Oates
Keyword(s):  
Inbred Mouse ◽  
Mouse Strains ◽  
Inbred Mouse Strains ◽  
Susceptibility And Resistance

Differential Maintenance and Frequency-Dependent Tuning of LTP at Hippocampal Synapses of Specific Strains of Inbred Mice

2000 ◽  
Vol 84 (5) ◽  
pp. 2484-2493 ◽  
Author(s):  
Peter V. Nguyen ◽  
Steven N. Duffy ◽  
Jennie Z. Young
Keyword(s):  
Genetic Background ◽  
Pyramidal Neurons ◽  
Inbred Mice ◽  
Inbred Mouse ◽  
Mouse Strains ◽  
Synaptic Facilitation ◽  
Ca1 Pyramidal Neurons ◽  
Hippocampal Synapses ◽  
Strain Dependent

Transgenic and knockout mice are used extensively to elucidate the molecular mechanisms of hippocampal synaptic plasticity. However, genetic and phenotypic variations between inbred mouse strains that are used to construct genetic models may confound the interpretation of cellular neurophysiological data derived from these models. Using in vitro slice stimulation and recording methods, we compared the membrane biophysical, cellular electrophysiological, and synaptoplastic properties of hippocampal CA1 neurons in four specific strains of inbred mice: C57BL/6J, CBA/J, DBA/2J, and 129/SvEms/J. Hippocampal long-term potentiation (LTP) induced by theta-pattern stimulation, and by repeated multi-burst 100-Hz stimulation at various interburst intervals, was better maintained in area CA1 of slices from BL/6J mice than in slices from CBA and DBA mice. At an interburst interval of 20 s, maintenance of LTP was impaired in CBA and DBA slices, as compared with BL/6J slices. When the interburst interval was reduced to 3 s, induction of LTP was significantly enhanced in129/SvEms slices, but not in DBA and CBA slices. Long-term depression (LTD) was not significantly different between slices from these four strains. For the four strains examined, CA1 pyramidal neurons showed no significant differences in spike-frequency accommodation, membrane input resistance, and number of spikes elicited by current injection. Synaptically-evoked glutamatergic postsynaptic currents did not significantly differ among CA1 pyramidal neurons in these four strains. Since the observed LTP deficits resembled those previously seen in transgenic mice with reduced hippocampal cAMP-dependent protein kinase (PKA) activity, we searched for possible strain-dependent differences in cAMP-dependent synaptic facilitation induced by forskolin (an activator of adenylate cyclase) and IBMX (a phosphodiesterase inhibitor). We found that forskolin/IBMX-induced synaptic facilitation was deficient in area CA1 of DBA/2J and CBA/J slices, but not in BL/6J and 129/SvEms/J slices. These defects in cAMP-induced synaptic facilitation may underlie the deficits in memory, observed in CBA/J and DBA/2J mice, that have been previously reported. We conclude that hippocampal LTP is influenced by genetic background and by the temporal characteristics of the stimulation protocol. The plasticity of hippocampal synapses in some inbred mouse strains may be “tuned” to particular temporal patterns of synaptic activity. From a broader perspective, our data support the notion that strain-dependent variation in genetic background is an important factor that can influence the synaptoplastic phenotypes observed in studies that use genetically modified mice to explore the molecular bases of synaptic plasticity.

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