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Infection and Immunity, December 2006, p. 6590-6598, Vol. 74, No. 12
0019-9567/06/$08.00+0     doi:10.1128/IAI.00868-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Mac-1+ Cells Are the Predominant Subset in the Early Hepatic Lesions of Mice Infected with Francisella tularensis{triangledown}

John W. Rasmussen,1 Jeronimo Cello,1 Horacio Gil,1,{dagger} Colin A. Forestal,1 Martha B. Furie,1,2,3 David G. Thanassi,1,3 and Jorge L. Benach1,3*

Center for Infectious Diseases,1 Department of Pathology,2 Department of Molecular Genetics and Microbiology, Stony Brook University, Stony Brook, New York 117943

Received 31 May 2006/ Returned for modification 7 July 2006/ Accepted 17 September 2006

The cell composition of early hepatic lesions of experimental murine tularemia has not been characterized with specific markers. The appearance of multiple granulomatous-necrotic lesions in the liver correlates with a marked increase in the levels of serum alanine transferase and lactate dehydrogenase. Francisella tularensis, detected by specific antibodies, can be first noted by day 1 and becomes associated with the lesions by 5 days postinoculation. These lesions become necrotic, with some evidence of in situ apoptosis. The lesions do not contain B, T, or NK cells. Rather, the lesions are largely composed of two subpopulations of Mac-1+ cells that are associated with the bacteria. Gr-1+ Mac-1+ immature myeloid cells and major histocompatibility complex class II-positive (MHC-II+) Mac-1+ macrophages were the most abundant cell phenotypes found in the granuloma and are likely major contributors in controlling the infection in its early stages. Our findings have shown that there is an early development of hepatic lesions where F. tularensis colocalizes with both Gr-1+ Mac-1+ and MHC-II+ Mac-1+ cells.

* Corresponding author. Mailing address: Center for Infectious Diseases, 5120 Centers for Molecular Medicine, Stony Brook, NY 11794-5120. Phone: (631) 632-4225. Fax: (631) 632-4294. E-mail: jbenach{at}notes.cc.sunysb.edu.

{triangledown} Published ahead of print on 25 September 2006.

Editor: J. T. Barbieri

{dagger} Present address: Laboratorio de Espiroquetas y Patógenos Especiales, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda 28220, Spain.

Infection and Immunity, December 2006, p. 6590-6598, Vol. 74, No. 12
0019-9567/06/$08.00+0     doi:10.1128/IAI.00868-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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