Toll-like receptor 4-positive macrophages protect mice from Pasteurella pneumotropica-induced pneumonia.
This study investigates Toll-like receptor 4 (TLR4)-positive macrophages in early recognition and clearance of pulmonary bacteria. TLR4 is a trans-membrane receptor that is the primary recognition molecule for lipopolysaccharide of gram-negative bacteria. The TLR4(Lps-del) mouse strains C57BL10/ScN (B10) and STOCK Abb(tm1) TLR4(Lps-del) Slc11a1(s)(B10 x C2D) are susceptible to pulmonary infections and develop pneumonia when naturally or experimentally infected by the opportunistic bacterium Pasteurella pneumotropica. Since these mice have the TLR4(Lps-del) genotype, we hypothesized that reconstitution of mice with TLR4-positive macrophages would provide resistance to this bacterium. A cultured macrophage cell line (C2D macrophages) and bone marrow cells from C2D mice were adoptively transferred to B10 and B10 x C2D mice by intraperitoneal injection. C2D macrophages increased B10 and B10 x C2D mouse resistance to P. pneumotropica. In C2D-recipient mice there was earlier transcription of tumor necrosis factor alpha and chemokines JE and macrophage inflammatory protein 2 (MIP-2) in the lungs of B10 and B10 x C2D mice, and there was earlier transcription of KC and MIP-1alpha in B10 x C2D mice. In addition, the course of inflammation following experimental Pasteurella challenge was altered in C2D recipients. C2D macrophages also protected B10 x C2D mice, which lack CD4(+) T cells. These data indicate that macrophages are critical for pulmonary immunity and can provide host resistance to P. pneumotropica. This study indicates that TLR4-positive macrophages are important for early recognition and clearance of pulmonary bacterial infections.
Hart
Marcia L
ML
Division of Biology, Kansas State University, Manhattan 66506, USA.
Mosier
Derek A
DA
Chapes
Stephen K
SK
D019264:Adoptive Transfer; D000818:Animals; D002460:Cell Line; D003433:Crosses, Genetic; D029721:Drosophila Proteins; D005802:Genes, MHC Class II; D020022:Genetic Predisposition to Disease; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D010325:Pasteurella / Q000472:pathogenicity*; D010326:Pasteurella Infections / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control; D018410:Pneumonia, Bacterial / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control*; D011956:Receptors, Cell Surface / Q000172:deficiency / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors
D029721:Drosophila Proteins; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors