YopH inhibits early pro-inflammatory cytokine responses during plague pneumonia.
BACKGROUND
Yersinia pestis is the causative agent of pneumonic plague; recently, we and others reported that during the first 24-36 hours after pulmonary infection with Y. pestis pro-inflammatory cytokine expression is undetectable in lung tissues.


RESULTS
Here, we report that, intranasal infection of mice with CO92 delta yopH mutant results in an early pro-inflammatory response in the lungs characterized by an increase in the pro-inflammatory cytokines Tumor Necrosis Factor-alpha and Interleukin one-beta 24 hours post-infection. CO92 delta yopH colonizes the lung but does not disseminate to the liver or spleen and is cleared from the host within 72 hours post-infection. This is different from what is observed in a wild-type CO92 infection, where pro-inflammatory cytokine expression and immune cell infiltration into the lungs is not detectable until 36-48 h post-infection. CO92 rapidly disseminates to the liver and spleen resulting in high bacterial burdens in these tissues ultimately cumulating in death 72-94 h post-infection. Mice deficient in TNF-alpha are more susceptible to CO92 delta yopH infection with 40% of the mice succumbing to infection.


CONCLUSIONS
Altogether, our results suggest that YopH can inhibit an early pro-inflammatory response in the lungs of mice and that this is an important step in the pathogenesis of infection.
Cantwell
Angelene M
AM
Department of Microbiology and Immunology, The University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA.
Bubeck
Sarah S
SS
Dube
Peter H
PH
D000281:Administration, Intranasal; D000818:Animals; D000906:Antibodies / Q000276:immunology; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology*; D001992:Bronchoalveolar Lavage Fluid / Q000382:microbiology; D016207:Cytokines / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D018836:Inflammation Mediators / Q000276:immunology*; D053583:Interleukin-1beta / Q000096:biosynthesis; D008168:Lung / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D051379:Mice; D009154:Mutation / Q000235:genetics; D010930:Plague / Q000276:immunology* / Q000382:microbiology* / Q000473:pathology; D017027:Protein Tyrosine Phosphatases / Q000172:deficiency / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000172:deficiency; D014774:Virulence / Q000276:immunology; D015010:Yersinia pestis / Q000201:enzymology / Q000276:immunology* / Q000472:pathogenicity
D000906:Antibodies; D001425:Bacterial Outer Membrane Proteins; D016207:Cytokines; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D014409:Tumor Necrosis Factor-alpha; D017027:Protein Tyrosine Phosphatases; C067571:yopH protein, Yersinia