Critical protective role for MCP-1 in pneumonic burkholderia mallei infection

Goodyear, Andrew, Jones, Abby, Troyer, Ryan, Bielefeldt-Ohmann, Helle and Dow, Steven (2010) Critical protective role for MCP-1 in pneumonic burkholderia mallei infection. Journal of Immunology, 184 3: 1445-1454. doi:10.4049/jimmunol.0900411

Author Goodyear, Andrew
Jones, Abby
Troyer, Ryan
Bielefeldt-Ohmann, Helle
Dow, Steven
Title Critical protective role for MCP-1 in pneumonic burkholderia mallei infection
Journal name Journal of Immunology   Check publisher's open access policy
ISSN 0022-1767
Publication date 2010-02
Sub-type Article (original research)
DOI 10.4049/jimmunol.0900411
Volume 184
Issue 3
Start page 1445
End page 1454
Total pages 10
Place of publication Poznan, Poland
Publisher Termedia sp. z o.o.
Language eng
Formatted abstract
Burkholderia mallei is a Gram-negative bacterial pathogen of domestic equidae and humans that can cause severe, rapidly life-threatening pneumonic infections. Little is known regarding the role of chemokines and early cellular immune responses in protective immunity to pulmonary infection with B. mallei. Although the role of MCP-1 in Gram-positive bacterial infections has been previously investigated, the role of MCP-1 in immunity to acute pneumonia caused by Gram-negative bacteria, such as B. mallei, has not been assessed. In a mouse model of pneumonic B. mallei infection, we found that both MCP-1-/- mice and CCR2-/- mice were extremely susceptible to pulmonary infection with B. mallei, compared with wild-type (WT) C57Bl/6 mice. Bacterial burden and organ lesions were significantly increased in CCR2-/- mice, compared with WT animals, following B. mallei challenge. Monocyte and dendritic cell recruitment into the lungs of CCR2-/- mice was significantly reduced in comparison with that in WT mice following B. mallei infection, whereas neutrophil recruitment was actually increased. Depletion of monocytes and macrophages prior to infection also greatly raised the susceptibility of WT mice to infection. Production of IL-12 and IFN-γ in the lungs after B. mallei infection was significantly impaired in both MCP-1-/- and CCR2-/- mice, whereas treatment of CCR2 -/- mice with rIFN-γ restored protection against lethal challenge with B. mallei. Thus, we conclude that MCP-1 plays a key role in regulating cellular immunity and IFN-γ production following pneumonic infection with B. mallei and therefore may also figure importantly in other Gram-negative pneumonias.
Keyword Monocyte Chemoattractant Protein-1
Innate Immune-Responses
Dendritic Cells
Pseudomallei Infection
Acute Toxoplasmosis
References Published online before print 30 December 2009.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
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