Genetic susceptibility to respiratory syncytial virus infection in inbred mice

Stark, James M.; McDowell, Susan A.; Koenigsknecht, Vincent; Prows, Daniel R.; Leikauf, John; Vine, Ann Marie Le; Leikauf, George D.

doi:10.1002/jmv.2196

Cited by 74 publications

(88 citation statements)

References 62 publications

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“…2A, significant weight loss was observed for unimmunized animals or mice immunized either with UV-RSV or WT-BCG, as well as BCG-OVA (data not shown). These data are consistent with previous studies indicating that naive mice challenged with RSV can show significant weight loss as early as 24 h after infection (35)(36)(37). In sharp contrast, mice immunized with either BCG-N or BCG-M2 showed no significant weight loss after RSV challenge, similarly to uninfected mice (Fig.…”

Section: Resultssupporting

confidence: 93%

Protective T cell immunity against respiratory syncytial virus is efficiently induced by recombinant BCG

Bueno

González

Cautivo

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

109

155

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Section: Resultssupporting

confidence: 93%

Protective T cell immunity against respiratory syncytial virus is efficiently induced by recombinant BCG

Bueno

González

Cautivo

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

109

155

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“…In models of RSV disease, mice with different genetic backgrounds respond to RSV with strain-specific cytokines and pathophysiological responses (7,8). Our laboratory has previously shown that the up-regulation of IL-13 in RSV-infected BALB/c exacerbates mucus production, airway hyperreactivity, and airway inflammation (9 -11), whereas others have indicated that the age of infection can influence the production of IL-13 (12).…”

Section: R Espiratory Syncytial Virus (Rsv)mentioning

confidence: 99%

MyD88-Mediated Instructive Signals in Dendritic Cells Regulate Pulmonary Immune Responses during Respiratory Virus Infection

Rudd

Schaller

Smit

et al. 2007

The Journal of Immunology

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Respiratory syncytial virus (RSV) is the leading cause of respiratory disease in infants worldwide. The induction of innate immunity and the establishment of adaptive immune responses are influenced by the recognition of pathogen-associated molecular patterns by TLRs. One of the primary pathways for TLR activation is by MyD88 adapter protein signaling. The present studies indicate that MyD88 deficiency profoundly impacts the pulmonary environment in RSV-infected mice characterized by the accumulation of eosinophils and augmented mucus production. Although there was little difference in CD4 T cell accumulation, there was also a significant decrease in conventional dendritic cells recruitment to the lungs of MyD88−/− mice. The exacerbation of RSV pathophysiology in MyD88−/− mice was associated with an enhanced Th2 cytokine profile that contributed to an inappropriate immune response. Furthermore, bone marrow-derived dendritic cells (BMDC) isolated from MyD88−/− mice were incapable of producing two important Th1 instructive signals, IL-12 and delta-like4, upon RSV infection. Although MyD88−/− BMDCs infected with RSV did up-regulate costimulatory molecules, they did not up-regulate class II as efficiently and stimulated less IFN-γ from CD4+ T cells in vitro compared with wild-type BMDCs. Finally, adoptive transfer of C57BL/6 BMDCs into MyD88−/− mice reconstituted Th1 immune responses in vivo, whereas transfer of MyD88−/− BMDCs into wild-type mice skewed the RSV responses toward a Th2 phenotype. Taken together, our data indicate that MyD88-mediated pathways are essential for the least pathogenic responses to this viral pathogen through the regulation of important Th1-associated instructive signals.

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“…Because of this, the laboratory mouse has been the experimental model of choice to study pathogenesis of infection, including innate and acquired host defense mechanisms. Inbred mouse strains differ significantly in their degree of susceptibility to infection with various human bacterial (eg, Mycobacterium tuberculosis, 15,16 Salmonella enterica, 17 Streptococcus pyogenes, 18 Streptococcus pneumoniae 19 ), fungal (eg, Histoplasma capsulatum, 20 Aspergillus fumigatus 21 ), protozoan (eg, Leishmania major, 22 Plasmodium berghei, 23 Plasmodium chabaudi 24 ), helminthic (eg, Schistosoma mansoni 25,26 ) as well as viral (eg, respiratory syncytial virus 27,28 ) pathogens. This attribute has been exploited to identify novel loci influencing resistance/susceptibility to infection and to provide new insight on host mechanisms involved in response to those pathogens that ultimately affect the onset, progression, and outcome of the infection.…”

mentioning

confidence: 99%

Immunological Mechanisms Underlying the Genetic Predisposition to Severe Staphylococcus aureus Infection in the Mouse Model

Köckritz-Blickwede

Rohde

Oehmcke

et al. 2008

The American Journal of Pathology

122

130

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Host genetic variations play a significant role in conferring predisposition to infection. In this study, we examined the immune mechanisms underlying the host genetic predisposition to severe Staphylococcus aureus infection in different mouse strains. Whereas C57BL/6 mice were the most resistant in terms of control of bacterial growth and survival, A/J, DBA/2, and BALB/c mice were highly susceptible and succumbed to infection shortly after bacterial inoculation. Other strains (C3H/HeN, CBA, and C57BL/10) exhibited intermediate susceptibility levels. Susceptibility of mice to S. aureus was associated with an inability to limit bacterial growth in the kidneys and development of pathology. Resistance to S. aureus in C57BL/6 mice was dependent on innate immune mechanisms because Rag2-IL2R␥ ؊/؊ C57BL/6 mice, which are deficient in B, T, and NK cells, were also resistant to infection. Indeed, neutrophil depletion or inhibition of neutrophil recruitment rendered C57BL/6 mice completely susceptible to S. aureus, indicating that neutrophils are essential for the observed resistance. Although neutrophil function is not inhibited in A/J mice, expression of neutrophil chemoattractants KC and MIP-2 peaked earlier in the kidneys of C57BL/6 mice than in A/J mice, indicating that a delay in neutrophil recruitment to the site of infection may underlie the increased susceptibility of A/J mice to S.

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Genetic susceptibility to respiratory syncytial virus infection in inbred mice

Cited by 74 publications

References 62 publications

Protective T cell immunity against respiratory syncytial virus is efficiently induced by recombinant BCG

Protective T cell immunity against respiratory syncytial virus is efficiently induced by recombinant BCG

MyD88-Mediated Instructive Signals in Dendritic Cells Regulate Pulmonary Immune Responses during Respiratory Virus Infection

Immunological Mechanisms Underlying the Genetic Predisposition to Severe Staphylococcus aureus Infection in the Mouse Model

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