Genetic control of macrophage susceptibility to infection by Legionella pneumophila

Yamamoto, Y

doi:10.1016/0378-1097(92)90055-s

Cited by 6 publications

(7 citation statements)

References 15 publications

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“…Interestingly, the dot/icm genes delay uptake and induce macropinocytosis in A/J mouse macrophages [14]. With the exception of A/J mice, most of the inbred mouse strains are not permissive to L. pneumophila infection; neither are macrophages isolated from these mice [40,41]. Macropinosomes containing L. pneumophila in A/J mouse macrophages are induced transiently and shrink rapidly (5-15 min) [14], and this mode of uptake is linked to the lgn1 locus on chromosome 13 of mice [14,42,43].…”

Section: Adherence and Entry Into Mammalian Cellsmentioning

confidence: 98%

Cell biology of the intracellular infection by Legionella pneumophila

Molmeret

Bitar

Han

et al. 2004

Microbes and Infection

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Section: Adherence and Entry Into Mammalian Cellsmentioning

confidence: 98%

Cell biology of the intracellular infection by Legionella pneumophila

Molmeret

Bitar

Han

et al. 2004

Microbes and Infection

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“…Macrophages derived from many inbred mouse strains have been shown to be restrictive or permissive of L. pneumophila intracellular growth, with the C57BL/6J (B6) strain being used as the canonical restrictive strain (9,42,43). A/J, a permissive mouse strain, supports 10 3 -to 10 4 -fold growth of L. pneumophila over a 3-day period, whereas B6 rarely supports Ͻ10-fold growth over this time period (9,42,43).…”

mentioning

confidence: 99%

“…A/J, a permissive mouse strain, supports 10 3 -to 10 4 -fold growth of L. pneumophila over a 3-day period, whereas B6 rarely supports Ͻ10-fold growth over this time period (9,42,43). Studies involving crosses of B6 and A/J showed that restriction of L. pneumophila growth is dominant and segregates in a Mendelian fashion via a single autosomal locus on mouse chromosome 13 named Lgn1 (5,9).…”

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confidence: 99%

A Hemidominant Naip5 Allele in Mouse Strain MOLF/Ei-Derived Macrophages Restricts Legionella pneumophila Intracellular Growth

Losick¹,

Stephan

Smirnova

et al. 2009

Infect Immun

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Mouse-derived macrophages have the unique ability to restrict or permit Legionella pneumophila intracellular growth. The common inbred mouse strain C57BL/6J (B6) restricts L. pneumophila growth, whereas macrophages derived from A/J mice allow >10 3 -fold bacterial growth within three days. This phenotypic difference was mapped to the mouse Naip5 allele. The B6 restrictive Naip5 allele is dominant, and six amino acid changes in its product were predicted to control permissiveness. By using the wild-derived mouse strain MOLF/Ei, we found that MOLF/Ei-derived macrophages also restrict L. pneumophila growth, yet the Naip5 protein is identical to the A/J Naip5 at the six-amino-acid signature. The MOLF/Ei restrictive trait, unlike that of B6-derived macrophages, was not dominant over the A/J trait. In spite of this phenotypic difference, the L. pneumophila growth restriction in MOLF/Ei macrophages was mapped to the Naip5 region as well, indicating that the originally predicted change in the A/J Naip5 allele may not be critical for restriction. In the product of the A/J Naip5 permissive allele, there are four unique amino acid changes that map to a NACHT-like domain. Similar misregulating mutations have been identified in the NACHT domains of Nod-like receptor (NLR) proteins. Therefore, one of these mutations may be critical for restriction of L. pneumophila intracellular growth, and this parallels results found with human NLR variants with defects in the innate immune response.

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“…Summersgill et al [10] found that induced nitric oxide synthase activity in RAW 264.7 cells, a murine macrophage cell line, was correlated with killing of L. pneumophila and depletion of intracellular iron. Since the mechanism explaining the differences in susceptibility among macrophages from different mouse strains remains to be determined [11,12], we studied the role of iron in macrophages from two mouse strains which differ in permissiveness to intracellular L. pneumophila growth.…”

Section: Introductionmentioning

confidence: 99%

Differences and similarities in permissive A/J versus non-permissive BALB/c murine macrophages infected with Legionella pneumophila: The role of iron

Gebran¹

1994

FEMS Immunology and Medical Microbiology

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Legionella pneumophila, a facultative intracellular pathogen, replicates within and kills thioglycolate-elicited (TG) macrophages from A/J mice, while growth is inhibited in TG macrophages from BALB/c mice which show no impaired viability. The role of iron in BALB/c and A/J macrophages regarding their permissiveness to L. pneumophila intracellular growth was investigated. We previously reported that TG macrophages from the A/J mouse strain readily supported the intracellular growth of L. pneumophila, while resident macrophages from the same strain of mice were not permissive. Recently we also found that such a difference in permissiveness between both A/J macrophage populations may be explained, at least in part, to intracellular availability of iron. In this report, differences in permissiveness to L. pneumophila growth between A/J TG macrophages and BALB/c TG macrophages was not due to intracellular iron availability. BALB/c and A/J TG macrophages exhibited similar expression of transferrin receptor and cellular iron content. The treatment of BALB/c TG macrophages with different iron compounds, namely ferric nitrilotriacetate (12.5-100 microM), ferric citrate (12.5-100 microM) and transferrin (0.5-5 mg ml-1), did not stimulate the intracellular proliferation of L. pneumophila. The reduction of intracellular iron availability by treatment with antibodies against transferrin receptor or with desferrioxamine suppressed the growth of L. pneumophila within BALB/c TG macrophages, suggesting that these cells do not restrict L. pneumophila growth because of iron. The production of nitric oxide was also similar in both macrophage populations, as measured by the Griess reaction. However, the synthesis of oxygen reactive species was three times higher in non-permissive BALB/c macrophages.(ABSTRACT TRUNCATED AT 250 WORDS)

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Genetic control of macrophage susceptibility to infection by Legionella pneumophila

Cited by 6 publications

References 15 publications

Cell biology of the intracellular infection by Legionella pneumophila

Cell biology of the intracellular infection by Legionella pneumophila

A Hemidominant Naip5 Allele in Mouse Strain MOLF/Ei-Derived Macrophages Restricts Legionella pneumophila Intracellular Growth

Differences and similarities in permissive A/J versus non-permissive BALB/c murine macrophages infected with Legionella pneumophila: The role of iron

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