Contribution of NK cells to the innate phase of host protection against an intracellular bacterium targeting systemic endothelium

Rong Fang, Nahed Ismail, David Walker

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

We investigated the mechanisms by which natural killer (NK) cells mediate innate host defense against infection with an endothelium-targeting intracellular bacterium, Rickettsia. We found that a robust Rickettsia-induced innate response in resistant mice cleared the bacteria early in the infection and was associated with significantly higher frequencies of splenic interferon (IFN)-γ (+) CD8 + T cells and cytotoxic NK cells compared with susceptible mice. More importantly, NK cell-deficient Rag -/-γc -/- animals displayed significantly increased susceptibility to Rickettsia infection compared with NK cell-sufficient Rag -/- mice, as evidenced by impaired bacterial clearance, early development of severe thrombosis in the liver, and a decreased serum level of IFN-γ. Furthermore, the lack of NK cells also impaired host resistance of CB-17 scid mice to Rickettsia, similar to what was observed in Rag -/-γc -/- mice. Interestingly, perforin deficiency in Rag -/-Prf1 -/- mice resulted in greater thrombosis and insignificantly different systemic levels of IFN-γ compared with Rag -/- mice, suggesting that perforin, which is mainly produced by NK cells, is involved in the prevention of vascular damage. Together, these findings reveal that NK cells mediate the innate phase of host protection against infection with rickettsiae, most likely via IFN-γ production. Furthermore, NK cells are involved in preventing rickettsial infection-induced endothelial cell damage, possibly via perforin production.

Original languageEnglish (US)
Pages (from-to)185-195
Number of pages11
JournalAmerican Journal of Pathology
Volume181
Issue number1
DOIs
StatePublished - Jul 2012

Fingerprint

Natural Killer Cells
Endothelium
Bacteria
Rickettsia
Interferons
Rickettsia Infections
Perforin
Thrombosis
Infection
Blood Vessels
Endothelial Cells
T-Lymphocytes
Liver
Serum

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

@article{f9eb817bef7e45d9a4b4a60e86c33041,
title = "Contribution of NK cells to the innate phase of host protection against an intracellular bacterium targeting systemic endothelium",
abstract = "We investigated the mechanisms by which natural killer (NK) cells mediate innate host defense against infection with an endothelium-targeting intracellular bacterium, Rickettsia. We found that a robust Rickettsia-induced innate response in resistant mice cleared the bacteria early in the infection and was associated with significantly higher frequencies of splenic interferon (IFN)-γ (+) CD8 + T cells and cytotoxic NK cells compared with susceptible mice. More importantly, NK cell-deficient Rag -/-γc -/- animals displayed significantly increased susceptibility to Rickettsia infection compared with NK cell-sufficient Rag -/- mice, as evidenced by impaired bacterial clearance, early development of severe thrombosis in the liver, and a decreased serum level of IFN-γ. Furthermore, the lack of NK cells also impaired host resistance of CB-17 scid mice to Rickettsia, similar to what was observed in Rag -/-γc -/- mice. Interestingly, perforin deficiency in Rag -/-Prf1 -/- mice resulted in greater thrombosis and insignificantly different systemic levels of IFN-γ compared with Rag -/- mice, suggesting that perforin, which is mainly produced by NK cells, is involved in the prevention of vascular damage. Together, these findings reveal that NK cells mediate the innate phase of host protection against infection with rickettsiae, most likely via IFN-γ production. Furthermore, NK cells are involved in preventing rickettsial infection-induced endothelial cell damage, possibly via perforin production.",
author = "Rong Fang and Nahed Ismail and David Walker",
year = "2012",
month = "7",
doi = "10.1016/j.ajpath.2012.03.020",
language = "English (US)",
volume = "181",
pages = "185--195",
journal = "American Journal of Pathology",
issn = "0002-9440",
publisher = "Elsevier Inc.",
number = "1",

}

TY - JOUR

T1 - Contribution of NK cells to the innate phase of host protection against an intracellular bacterium targeting systemic endothelium

AU - Fang, Rong

AU - Ismail, Nahed

AU - Walker, David

PY - 2012/7

Y1 - 2012/7

N2 - We investigated the mechanisms by which natural killer (NK) cells mediate innate host defense against infection with an endothelium-targeting intracellular bacterium, Rickettsia. We found that a robust Rickettsia-induced innate response in resistant mice cleared the bacteria early in the infection and was associated with significantly higher frequencies of splenic interferon (IFN)-γ (+) CD8 + T cells and cytotoxic NK cells compared with susceptible mice. More importantly, NK cell-deficient Rag -/-γc -/- animals displayed significantly increased susceptibility to Rickettsia infection compared with NK cell-sufficient Rag -/- mice, as evidenced by impaired bacterial clearance, early development of severe thrombosis in the liver, and a decreased serum level of IFN-γ. Furthermore, the lack of NK cells also impaired host resistance of CB-17 scid mice to Rickettsia, similar to what was observed in Rag -/-γc -/- mice. Interestingly, perforin deficiency in Rag -/-Prf1 -/- mice resulted in greater thrombosis and insignificantly different systemic levels of IFN-γ compared with Rag -/- mice, suggesting that perforin, which is mainly produced by NK cells, is involved in the prevention of vascular damage. Together, these findings reveal that NK cells mediate the innate phase of host protection against infection with rickettsiae, most likely via IFN-γ production. Furthermore, NK cells are involved in preventing rickettsial infection-induced endothelial cell damage, possibly via perforin production.

AB - We investigated the mechanisms by which natural killer (NK) cells mediate innate host defense against infection with an endothelium-targeting intracellular bacterium, Rickettsia. We found that a robust Rickettsia-induced innate response in resistant mice cleared the bacteria early in the infection and was associated with significantly higher frequencies of splenic interferon (IFN)-γ (+) CD8 + T cells and cytotoxic NK cells compared with susceptible mice. More importantly, NK cell-deficient Rag -/-γc -/- animals displayed significantly increased susceptibility to Rickettsia infection compared with NK cell-sufficient Rag -/- mice, as evidenced by impaired bacterial clearance, early development of severe thrombosis in the liver, and a decreased serum level of IFN-γ. Furthermore, the lack of NK cells also impaired host resistance of CB-17 scid mice to Rickettsia, similar to what was observed in Rag -/-γc -/- mice. Interestingly, perforin deficiency in Rag -/-Prf1 -/- mice resulted in greater thrombosis and insignificantly different systemic levels of IFN-γ compared with Rag -/- mice, suggesting that perforin, which is mainly produced by NK cells, is involved in the prevention of vascular damage. Together, these findings reveal that NK cells mediate the innate phase of host protection against infection with rickettsiae, most likely via IFN-γ production. Furthermore, NK cells are involved in preventing rickettsial infection-induced endothelial cell damage, possibly via perforin production.

UR - http://www.scopus.com/inward/record.url?scp=84862662715&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84862662715&partnerID=8YFLogxK

U2 - 10.1016/j.ajpath.2012.03.020

DO - 10.1016/j.ajpath.2012.03.020

M3 - Article

C2 - 22617213

AN - SCOPUS:84862662715

VL - 181

SP - 185

EP - 195

JO - American Journal of Pathology

JF - American Journal of Pathology

SN - 0002-9440

IS - 1

ER -