Investigation of the role of macrophages and endogenous interferon-γ in natural resistance of mice against Legionella pneumophila infection

Fujio, H

doi:10.1016/0378-1097(92)90115-5

Cited by 9 publications

(9 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Interestingly, addition of anti-IFN-␥ to these cells further increased their ability to support bacterial growth, suggesting that autocrine IFN-␥ is also important in conferring resistance to infection in aged macrophages (6,7). Consistent with this, we found that IFN-␥ was present in supernatants of aged cells before infection even in higher amounts with respect to those found in fresh macrophage cultures (data not shown).…”

Section: Discussionsupporting

confidence: 78%

“…If not otherwise stated, macrophage monolayers (ϳ10 6 cells per well, in 96 flat-bottom plates) were infected with 5 ϫ 10 4 bacteria per well (0.05 multiplicity of infection (m.o.i.)). Infection was performed as follows: cell monolayers were washed and infected in triplicate with L. pneumophila for 2 h at 37°C.…”

Section: Infection and Enumeration Of L Pneumophilamentioning

confidence: 99%

See 1 more Smart Citation

Type I IFN Protects Permissive Macrophages fromLegionella pneumophilaInfection through an IFN-γ-Independent Pathway

Schiavoni¹,

Mauri

Carlei³

et al. 2004

The Journal of Immunology

View full text Add to dashboard Cite

Legionella pneumophila is an intracellular pathogen whose replication in macrophages is mainly controlled by IFN-γ. Freshly isolated peritoneal macrophages elicited in vivo with thioglycolate (TG) from A/J mice are highly permissive to L. pneumophila growth in vitro, while TG-elicited macrophages from CD1 mice are resistant. In this study, we show that when CD1 TG-macrophages are cultured for 7 days, they become permissive to Legionella infection. We demonstrate that treatment with type I IFN (IFN-αβ) totally inhibits the growth of L. pneumophila in both freshly isolated A/J and in vitro-aged CD1 TG-macrophages. IFN-αβ protective effect on permissive macrophages was comparable to that induced by IFN-γ. Even low doses of either IFN-α or IFN-β alone were effective in inhibiting L. pneumophila multiplication in macrophage cultures. Notably, treatment of resistant, freshly isolated CD1 TG-macrophages with Ab to mouse IFN-αβ significantly enhanced their susceptibility to Legionella infection in vitro, thus implying a role of endogenous IFN-αβ in mediating the natural resistance of macrophages to L. pneumophila infection. Finally, addition of anti-IFN-γ-neutralizing Ab did not restore Legionella growth in IFN-α- or IFN-β-treated A/J or CD1 permissive macrophages, indicating that IFN-αβ effect was not mediated by IFN-γ. This observation was further confirmed by the finding that IFN-αβ was effective in inhibiting L. pneumophila replication in macrophages from IFN-γ receptor-deficient mice. Taken together, our results provide the first evidence for a role of IFN-αβ in the control of L. pneumophila infection in mouse models of susceptible macrophages and suggest the existence of different pathways for the control of intracellular bacteria in macrophages.

show abstract

Section: Discussionsupporting

confidence: 78%

Section: Infection and Enumeration Of L Pneumophilamentioning

confidence: 99%

Type I IFN Protects Permissive Macrophages fromLegionella pneumophilaInfection through an IFN-γ-Independent Pathway

Schiavoni¹,

Mauri

Carlei³

et al. 2004

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…These in vitro phenotypes were found to be Myd88 (and likely also TLR5)-independent. Although Naip5 regulates intracellular multiplication of Legionella within macrophages in vitro, its effect on in vivo replication is considerably less dramatic, varying from negligible to ϳ10-fold differences in lung CFUs (7,9,40,41). In addition to NAIP5, IPAF has also been found to mediate recognition of Lp flagellin with TLR5-independent activation of caspase-1 and restriction of Lp replication (9,10).…”

Section: Discussionmentioning

confidence: 99%

Altered Inflammatory Responses in TLR5-Deficient Mice Infected with Legionella pneumophila

Hawn

Berrington

Smith

et al. 2007

The Journal of Immunology

107

View full text Add to dashboard Cite

Legionella pneumophila (Lp), an important cause of morbidity and mortality from pneumonia, infects alveolar macrophages (AMs) and is recognized by several TLRs as well as Birc1e (NAIP5) and IL-1 converting enzyme-protease activating factor. We examined the role of TLR5 during the murine response to aerosolized Lp infection. At 4 h after infection, Tlr5−/− mice had lower numbers of polymorphonuclear neutrophils (PMNs) in their broncho-alveolar lavage fluid in comparison to wild-type (WT) mice. At 24 and 72 h, the PMN recruitment was similar. WT mice infected with a flagellin-deficient strain (LpFlaA−) also showed an impaired early PMN response at 4 h compared with those infected with the WT strain. There was no consistent difference in bacterial counts at any of the time points when comparing the Tlr5−/− and WT mice. However, at 6 days after infection, the Tlr5−/− mice had increased leukocytic infiltrates in the alveolar and peribronchial interstitial spaces that were consistent with organizing pneumonia. We also examined the role of TLR5 during macrophage infection. In contrast to bone marrow-derived macrophages, AMs secreted TNF-α after stimulation with purified flagellin. In addition, WT, but not Tlr5−/−, AMs produced TNF-α after stimulation with Lp. Live LpFlaA− did not induce TNF-α secretion in AM. These results suggested that AMs recognize Lp flagellin and that a majority of the Lp-induced TNF-α response is TLR5-mediated. Thus, TLR5 mediates recognition of Lp in AMs and performs a distinct role during the in vivo pulmonary immune response through regulation of early PMN recruitment and subsequent later development of pneumonia.

show abstract

“…Bone marrow-derived macrophages and explanted alveolar macrophages were obtained from A/J mice and infected with L. pneumophila as previously described (29,41,91). Briefly, monolayers consisting of 1.0 ϫ 10 5 to 2.5 ϫ 10 5 macrophages were infected with bacteria at a multiplicity of infection equal to 1 (for bone marrow-derived cells) or 5 (for alveolar cells), incubated for 2 h to allow bacterial entry, and then washed three times with media to remove unincorporated bacteria.…”

Section: Methodsmentioning

confidence: 99%

Purification of Legiobactin and Importance of This Siderophore in Lung Infection byLegionella pneumophila

Allard

Dao

Sanjeevaiah³

et al. 2009

Infect Immun

View full text Add to dashboard Cite

When cultured in a low-iron medium, Legionella pneumophila secretes a siderophore (legiobactin) that is both reactive in the chrome azurol S (CAS) assay and capable of stimulating the growth of iron-starved legionellae. Using anion-exchange high-pressure liquid chromatography (HPLC), we purified legiobactin from culture supernatants of a virulent strain of L. pneumophila. In the process, we detected the ferrated form of legiobactin as well as other CAS-reactive substances. Purified legiobactin had a yellow-gold color and absorbed primarily from 220 nm and below. In accordance, nuclear magnetic resonance spectroscopy revealed that legiobactin lacks aromatic carbons, and among the 13 aliphatics present, there were 3 carbonyls. When examined by HPLC, supernatants from L. pneumophila mutants inactivated for lbtA and lbtB completely lacked legiobactin, indicating that the LbtA and LbtB proteins are absolutely required for siderophore activity. Independently derived lbtA mutants, but not a complemented derivative, displayed a reduced ability to infect the lungs of A/J mice after intratracheal inoculation, indicating that legiobactin is required for optimal intrapulmonary survival by L. pneumophila. This defect, however, was not evident when the lbtA mutant and its parental strain were coinoculated into the lung, indicating that legiobactin secreted by the wild type can promote growth of the mutant in trans. Legiobactin mutants grew normally in murine lung macrophages and alveolar epithelial cells, suggesting that legiobactin promotes something other than intracellular infection of resident lung cells. Overall, these data represent the first documentation of a role for siderophore expression in the virulence of L. pneumophila.

show abstract

Investigation of the role of macrophages and endogenous interferon-γ in natural resistance of mice against Legionella pneumophila infection

Cited by 9 publications

References 18 publications

Type I IFN Protects Permissive Macrophages fromLegionella pneumophilaInfection through an IFN-γ-Independent Pathway

Type I IFN Protects Permissive Macrophages fromLegionella pneumophilaInfection through an IFN-γ-Independent Pathway

Altered Inflammatory Responses in TLR5-Deficient Mice Infected with Legionella pneumophila

Purification of Legiobactin and Importance of This Siderophore in Lung Infection byLegionella pneumophila

Contact Info

Product

Resources

About