Myd88-dependent recruitment of monocytes and dendritic cells required for protection from pulmonary Burkholderia mallei infection

Goodyear, Andrew, Troyer, Ryan, Bielefeldt-Ohmann, Helle and Dow, Steven (2012) Myd88-dependent recruitment of monocytes and dendritic cells required for protection from pulmonary Burkholderia mallei infection. Infection and Immunity, 80 1: 110-120. doi:10.1128/IAI.05819-11

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Author Goodyear, Andrew
Troyer, Ryan
Bielefeldt-Ohmann, Helle
Dow, Steven
Title Myd88-dependent recruitment of monocytes and dendritic cells required for protection from pulmonary Burkholderia mallei infection
Formatted title
Myd88-dependent recruitment of monocytes and dendritic cells required for protection from pulmonary Burkholderia mallei infection
Journal name Infection and Immunity   Check publisher's open access policy
ISSN 1098-5522
1070-6313
Publication date 2012-01
Year available 2011
Sub-type Article (original research)
DOI 10.1128/IAI.05819-11
Open Access Status File (Publisher version)
Volume 80
Issue 1
Start page 110
End page 120
Total pages 11
Place of publication Washington, DC, United States
Publisher American Society for Microbiology
Collection year 2012
Language eng
Formatted abstract
The Gram-negative bacterium Burkholderia mallei causes rapidly fatal illness in equines and humans when contracted by inhalation and also has the potential to be used as a bioweapon. However, little is known regarding the early innate immune responses and signaling mechanisms required to generate protection from pneumonic B. mallei infection. We showed previously that monocyte chemoattractant protein 1 (MCP-1) was a critical chemokine required for protection from pneumonic B. mallei infection. We have now extended those studies to identify key Toll-like receptor (TLR) signaling pathways, effector cells, and cytokines required for protection from respiratory B. mallei infection. We found that MyD88−/− mice were highly susceptible to pulmonary challenge with B. mallei and had significantly short survival times, increased bacterial burdens, and severe organ pathology compared to wild-type mice. Notably, MyD88−/− mice had significantly fewer monocytes and dendritic cells (DCs) in lung tissues and airways than infected wild-type mice despite markedly higher bacterial burdens. The MyD88−/− mice were also completely unable to produce gamma interferon (IFN-γ) at any time points following infection. In wild-type mice, NK cells were the primary cells producing IFN-γ in the lungs following B. mallei infection, while DCs and monocytes were the primary cellular sources of interleukin-12 (IL-12) production. Treatment with recombinant IFN-γ (rIFN-γ) was able to significantly restore protective immunity in MyD88−/− mice. Thus, we conclude that the MyD88-dependent recruitment of inflammatory monocytes and DCs to the lungs and the local production of IL-12, followed by NK cell production of IFN-γ, are the key initial cellular responses required for early protection from B. mallei infection.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Published ahead of print 24 October 2011

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2012 Collection
School of Veterinary Science Publications
 
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Citation counts: TR Web of Science Citation Count  Cited 11 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 10 times in Scopus Article | Citations
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