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Infection and Immunity, January 2007, p. 236-242, Vol. 75, No. 1
0019-9567/07/$08.00+0     doi:10.1128/IAI.01249-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Respiratory Tract Infection with Mycoplasma pneumoniae in Interleukin-12 Knockout Mice Results in Improved Bacterial Clearance and Reduced Pulmonary Inflammation{triangledown}

C. M. Salvatore,1 M. Fonseca-Aten,1 K. Katz-Gaynor,1 A. M. Gomez,3 A. Mejias,1 C. Somers,1 S. Chavez-Bueno,1 G. H. McCracken,1 and R. D. Hardy1,2*

Departments of Pediatric Infectious Diseases,1 Internal Medicine,2 Pathology, University of Texas Southwestern Medical Center, Dallas, Texas3

Received 4 August 2006/ Returned for modification 9 September 2006/ Accepted 13 October 2006

Mycoplasma pneumoniae is a leading cause of pneumonia and is associated with asthma. Evidence links M. pneumoniae respiratory disease severity with interleukin-12 (IL-12) concentration in respiratory secretions. We evaluated the microbiologic, inflammatory, and pulmonary function indices of M. pneumoniae pneumonia in IL-12 (p35) knockout (KO) mice and wild-type (WT) mice to determine the role of IL-12 in M. pneumoniae respiratory disease. Eight-week-old wild-type BALB/c mice and 8-week-old IL-12 (p35) KO BALB/c mice were inoculated once intranasally with 107 CFU of M. pneumoniae. Mice were evaluated at days 2, 4, and 7 after inoculation. Outcome variables included quantitative bronchoalveolar lavage (BAL) M. pneumoniae culture, lung histopathologic scores (HPS), BAL cytokine concentrations determined by enzyme-linked immunosorbent assay (tumor necrosis factor alpha [TNF-{alpha}], gamma interferon [IFN-{gamma}], IL-1ß, IL-2, IL-4, IL-5, IL-6, IL-10, and granulocyte-macrophage colony-stimulating factor) and plethysmography, before and after methacholine, to assess airway obstruction (AO) and airway hyperreactivity (AHR). IL-12 (p35) KO mice infected with M. pneumoniae were found to have significantly lower BAL M. pneumoniae concentrations compared with M. pneumoniae-infected WT mice. Lung HPS and the parenchymal pneumonia subscores (neutrophilic alveolar infiltrate), as well as AO, were significantly lower in infected KO mice. No difference was found for AHR. Infected KO mice had significantly lower BAL concentrations of IFN-{gamma} than WT mice; a trend toward lower BAL concentrations was observed for IL-10 (P = 0.065) and TNF-{alpha} (P = 0.078). No differences were found for IL-1ß, IL-2, IL-4, IL-5, or IL-6. The lack of IL-12 in experimental M. pneumoniae pneumonia was associated with less severe pulmonary disease and more rapid microbiologic and histologic resolution.

* Corresponding author. Mailing address: Department of Internal Medicine and Pediatric Infectious Diseases, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390-9063, Phone: (214) 648-3720. Fax: (214) 648-2961. E-mail: robert.hardy{at}UTSouthwestern.edu.

{triangledown} Published ahead of print on 30 October 2006.

Editor: J. L. Flynn

Infection and Immunity, January 2007, p. 236-242, Vol. 75, No. 1
0019-9567/07/$08.00+0     doi:10.1128/IAI.01249-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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