Macrophage Migration Inhibitory Factor Is Detrimental in Pneumococcal Pneumonia and a Target for Therapeutic Immunomodulation.
Mortality from pneumococcal pneumonia remains high despite antibiotic therapy, highlighting the pathogenic potential for host inflammation. We demonstrate that macrophage migration inhibitory factor (MIF), an innate immune mediator, is detrimental for survival and associated with lung pathology, inflammatory cellular infiltration, and bacterial replication in a mouse model of pneumococcal pneumonia, despite being necessary for clearance from the nasopharynx. Treatment of animals with a small-molecule inhibitor of MIF improves survival by reducing inflammation and improving bacterial control. Our work demonstrates that MIF modulates beneficial versus detrimental inflammatory responses in the host-pneumococcal interaction and is a potential target for therapeutic modulation.
Department of Microbiology.
Jeffrey N
JN
Weiser
Department of Microbiology.
Aoife M
AM
Roche
Department of Microbiology Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia.
Christopher B
CB
Hergott
Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia.
Meredith I
MI
LaRose
Department of Medicine, Yale School of Medicine.
Tarah
T
Connolly
Department of Chemistry, Yale University, New Haven, Connecticut.
William L
WL
Jorgensen
Department of Medicine, Yale School of Medicine.
Lin
L
Leng
Department of Medicine, Yale School of Medicine.
Richard
R
Bucala
Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia.
Rituparna
R
Das
D000818:Animals; D004195:Disease Models, Animal; D019746:Intramolecular Oxidoreductases / Q000378:metabolism*; D008168:Lung / Q000473:pathology*; D008263:Macrophage Migration-Inhibitory Factors / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D011018:Pneumonia, Pneumococcal / Q000276:immunology* / Q000473:pathology*; D016019:Survival Analysis
D008263:Macrophage Migration-Inhibitory Factors; D019746:Intramolecular Oxidoreductases; C076231:Mif protein, mouse
macrophage migration inhibitory factor; pneumococcus; pneumonia