| First Author | Goodyear A | Year | 2012 |
| Journal | Infect Immun | Volume | 80 |
| Issue | 1 | Pages | 110-20 |
| PubMed ID | 22025508 | Mgi Jnum | J:178961 |
| Mgi Id | MGI:5300674 | Doi | 10.1128/IAI.05819-11 |
| Citation | Goodyear A, et al. (2012) MyD88-Dependent Recruitment of Monocytes and Dendritic Cells Required for Protection from Pulmonary Burkholderia mallei Infection. Infect Immun 80(1):110-20 |
| abstractText | 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-gamma) at any time points following infection. In wild-type mice, NK cells were the primary cells producing IFN-gamma 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-gamma (rIFN-gamma) 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-gamma, are the key initial cellular responses required for early protection from B. mallei infection. |
