The p47 GTPases Iigp2 and Irgb10 regulate innate immunity and inflammation to murine Chlamydia psittaci infection

Isao Miyairi, Venkat R.R. Arva Tatireddigari, Olaimatu S. Mahdi, Lorne A. Rose, Robert J. Belland, Lu Lu, Robert Williams, Gerald I. Byrne

Research output: Contribution to journalArticle

61 Citations (Scopus)

Abstract

C57BL/6J mice were 10 5 -fold more resistant to Chlamydia psittaci infection than DBA/2J mice by LD 100 determinations. Linkage analysis using BXD recombinant inbred strains revealed a single effector locus at a 1.5-Mbp region on chromosome 11 encoding a cluster of three p47 GTPases (Irgb10, Igtp, and Iigp2). Western blots of infected tissue showed that Irgb10 was elevated in resistant mice and one of the two possible Iigp2 protein isoforms was preferentially expressed in susceptible mice. The BXD39 strain, susceptible at Irgb10 and resistant at Iigp2, had an intermediate phenotype implicating the nonredundant role of these p47 GTPases. C57BL/6J and DBA/2J exhibited a difference in IFN-γ-dependent chlamydial control, which was reversible by Iigp2 small interfering RNA knockdown. Microarrays of infected peritoneal lavage revealed >10-fold upregulation of neutrophil-recruiting chemokines in susceptible mice and >100-fold increase in macrophage differentiation genes in resistant mice, indicating that the susceptibility pattern involves the stimulation of different inflammatory cell-recruiting pathways. Massive neutrophil recruitment was seen in susceptible mice by histology and flow cytometry, and neutrophil chemokine receptor (CXCR2) knockout mice on a susceptible background survived a lethal challenge, confirming that neutrophil recruitment was required for susceptibility. Congenic Igtp knockout mice also susceptible at Irgb10 and Iigp2 on a resistant background recruited neutrophils and succumbed to infection. We conclude that Irgb10 and Iigp2 act together to confer differential susceptibility against murine chlamydial infection. Data indicate that these p47 GTPases have cellautonomous effects that result in vastly different inflammatory stimulations, leading to either recovery or death.

Original languageEnglish (US)
Pages (from-to)1814-1824
Number of pages11
JournalJournal of Immunology
Volume179
Issue number3
DOIs
StatePublished - Aug 1 2007

Fingerprint

Chlamydophila psittaci
Chlamydia Infections
GTP Phosphohydrolases
Innate Immunity
Inflammation
Neutrophils
Neutrophil Infiltration
Knockout Mice
Peritoneal Lavage
Inbred DBA Mouse
Chromosomes, Human, Pair 11
Chemokine Receptors
Infection
Inbred C57BL Mouse
Chemokines
Small Interfering RNA
Histology
Flow Cytometry
Protein Isoforms
Up-Regulation

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

Miyairi, I., Arva Tatireddigari, V. R. R., Mahdi, O. S., Rose, L. A., Belland, R. J., Lu, L., ... Byrne, G. I. (2007). The p47 GTPases Iigp2 and Irgb10 regulate innate immunity and inflammation to murine Chlamydia psittaci infection. Journal of Immunology, 179(3), 1814-1824. https://doi.org/10.4049/jimmunol.179.3.1814

The p47 GTPases Iigp2 and Irgb10 regulate innate immunity and inflammation to murine Chlamydia psittaci infection. / Miyairi, Isao; Arva Tatireddigari, Venkat R.R.; Mahdi, Olaimatu S.; Rose, Lorne A.; Belland, Robert J.; Lu, Lu; Williams, Robert; Byrne, Gerald I.

In: Journal of Immunology, Vol. 179, No. 3, 01.08.2007, p. 1814-1824.

Research output: Contribution to journalArticle

Miyairi, Isao ; Arva Tatireddigari, Venkat R.R. ; Mahdi, Olaimatu S. ; Rose, Lorne A. ; Belland, Robert J. ; Lu, Lu ; Williams, Robert ; Byrne, Gerald I. / The p47 GTPases Iigp2 and Irgb10 regulate innate immunity and inflammation to murine Chlamydia psittaci infection. In: Journal of Immunology. 2007 ; Vol. 179, No. 3. pp. 1814-1824.
@article{55391160953d4714941c9a6fa2f7aead,
title = "The p47 GTPases Iigp2 and Irgb10 regulate innate immunity and inflammation to murine Chlamydia psittaci infection",
abstract = "C57BL/6J mice were 10 5 -fold more resistant to Chlamydia psittaci infection than DBA/2J mice by LD 100 determinations. Linkage analysis using BXD recombinant inbred strains revealed a single effector locus at a 1.5-Mbp region on chromosome 11 encoding a cluster of three p47 GTPases (Irgb10, Igtp, and Iigp2). Western blots of infected tissue showed that Irgb10 was elevated in resistant mice and one of the two possible Iigp2 protein isoforms was preferentially expressed in susceptible mice. The BXD39 strain, susceptible at Irgb10 and resistant at Iigp2, had an intermediate phenotype implicating the nonredundant role of these p47 GTPases. C57BL/6J and DBA/2J exhibited a difference in IFN-γ-dependent chlamydial control, which was reversible by Iigp2 small interfering RNA knockdown. Microarrays of infected peritoneal lavage revealed >10-fold upregulation of neutrophil-recruiting chemokines in susceptible mice and >100-fold increase in macrophage differentiation genes in resistant mice, indicating that the susceptibility pattern involves the stimulation of different inflammatory cell-recruiting pathways. Massive neutrophil recruitment was seen in susceptible mice by histology and flow cytometry, and neutrophil chemokine receptor (CXCR2) knockout mice on a susceptible background survived a lethal challenge, confirming that neutrophil recruitment was required for susceptibility. Congenic Igtp knockout mice also susceptible at Irgb10 and Iigp2 on a resistant background recruited neutrophils and succumbed to infection. We conclude that Irgb10 and Iigp2 act together to confer differential susceptibility against murine chlamydial infection. Data indicate that these p47 GTPases have cellautonomous effects that result in vastly different inflammatory stimulations, leading to either recovery or death.",
author = "Isao Miyairi and {Arva Tatireddigari}, {Venkat R.R.} and Mahdi, {Olaimatu S.} and Rose, {Lorne A.} and Belland, {Robert J.} and Lu Lu and Robert Williams and Byrne, {Gerald I.}",
year = "2007",
month = "8",
day = "1",
doi = "10.4049/jimmunol.179.3.1814",
language = "English (US)",
volume = "179",
pages = "1814--1824",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "3",

}

TY - JOUR

T1 - The p47 GTPases Iigp2 and Irgb10 regulate innate immunity and inflammation to murine Chlamydia psittaci infection

AU - Miyairi, Isao

AU - Arva Tatireddigari, Venkat R.R.

AU - Mahdi, Olaimatu S.

AU - Rose, Lorne A.

AU - Belland, Robert J.

AU - Lu, Lu

AU - Williams, Robert

AU - Byrne, Gerald I.

PY - 2007/8/1

Y1 - 2007/8/1

N2 - C57BL/6J mice were 10 5 -fold more resistant to Chlamydia psittaci infection than DBA/2J mice by LD 100 determinations. Linkage analysis using BXD recombinant inbred strains revealed a single effector locus at a 1.5-Mbp region on chromosome 11 encoding a cluster of three p47 GTPases (Irgb10, Igtp, and Iigp2). Western blots of infected tissue showed that Irgb10 was elevated in resistant mice and one of the two possible Iigp2 protein isoforms was preferentially expressed in susceptible mice. The BXD39 strain, susceptible at Irgb10 and resistant at Iigp2, had an intermediate phenotype implicating the nonredundant role of these p47 GTPases. C57BL/6J and DBA/2J exhibited a difference in IFN-γ-dependent chlamydial control, which was reversible by Iigp2 small interfering RNA knockdown. Microarrays of infected peritoneal lavage revealed >10-fold upregulation of neutrophil-recruiting chemokines in susceptible mice and >100-fold increase in macrophage differentiation genes in resistant mice, indicating that the susceptibility pattern involves the stimulation of different inflammatory cell-recruiting pathways. Massive neutrophil recruitment was seen in susceptible mice by histology and flow cytometry, and neutrophil chemokine receptor (CXCR2) knockout mice on a susceptible background survived a lethal challenge, confirming that neutrophil recruitment was required for susceptibility. Congenic Igtp knockout mice also susceptible at Irgb10 and Iigp2 on a resistant background recruited neutrophils and succumbed to infection. We conclude that Irgb10 and Iigp2 act together to confer differential susceptibility against murine chlamydial infection. Data indicate that these p47 GTPases have cellautonomous effects that result in vastly different inflammatory stimulations, leading to either recovery or death.

AB - C57BL/6J mice were 10 5 -fold more resistant to Chlamydia psittaci infection than DBA/2J mice by LD 100 determinations. Linkage analysis using BXD recombinant inbred strains revealed a single effector locus at a 1.5-Mbp region on chromosome 11 encoding a cluster of three p47 GTPases (Irgb10, Igtp, and Iigp2). Western blots of infected tissue showed that Irgb10 was elevated in resistant mice and one of the two possible Iigp2 protein isoforms was preferentially expressed in susceptible mice. The BXD39 strain, susceptible at Irgb10 and resistant at Iigp2, had an intermediate phenotype implicating the nonredundant role of these p47 GTPases. C57BL/6J and DBA/2J exhibited a difference in IFN-γ-dependent chlamydial control, which was reversible by Iigp2 small interfering RNA knockdown. Microarrays of infected peritoneal lavage revealed >10-fold upregulation of neutrophil-recruiting chemokines in susceptible mice and >100-fold increase in macrophage differentiation genes in resistant mice, indicating that the susceptibility pattern involves the stimulation of different inflammatory cell-recruiting pathways. Massive neutrophil recruitment was seen in susceptible mice by histology and flow cytometry, and neutrophil chemokine receptor (CXCR2) knockout mice on a susceptible background survived a lethal challenge, confirming that neutrophil recruitment was required for susceptibility. Congenic Igtp knockout mice also susceptible at Irgb10 and Iigp2 on a resistant background recruited neutrophils and succumbed to infection. We conclude that Irgb10 and Iigp2 act together to confer differential susceptibility against murine chlamydial infection. Data indicate that these p47 GTPases have cellautonomous effects that result in vastly different inflammatory stimulations, leading to either recovery or death.

UR - http://www.scopus.com/inward/record.url?scp=34548644595&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34548644595&partnerID=8YFLogxK

U2 - 10.4049/jimmunol.179.3.1814

DO - 10.4049/jimmunol.179.3.1814

M3 - Article

VL - 179

SP - 1814

EP - 1824

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 3

ER -