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Infection and Immunity, August 2002, p. 4591-4599, Vol. 70, No. 8
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.8.4591-4599.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Tumor Necrosis Factor Alpha Stimulates Killing of Mycobacterium tuberculosis by Human Neutrophils

Kevin O. Kisich,1* Michael Higgins,2 Gill Diamond,3 and Leonid Heifets2

Departments of Immunology,1 Medicine, National Jewish Medical and Research Center, Denver, Colorado 80206,2 Department of Anatomy, Cell Biology, and Injury Sciences, University of Medicine and Dentistry of New JerseyNewark, New Jersey 071033

Received 25 October 2001/ Returned for modification 7 January 2002/ Accepted 26 April 2002

The ability of human neutrophils to aid in defense against pulmonary infection with Mycobacterium tuberculosis is controversial. In this study, we have shown that neutrophils respond to and phagocytose M. tuberculosis in human lesions. Neutrophils from healthy individuals were able to kill significant fractions of an inoculum of M. tuberculosis within 1 h of phagocytosis, and this ability was enhanced by tumor necrosis factor alpha but not by gamma interferon. The mycobactericidal mechanism was nonoxidative, as inhibitors of reactive oxygen or reactive nitrogen intermediates did not interfere with killing. However, the mycobactericidal mechanism was associated with increased exposure of intracellular M. tuberculosis to neutrophil defensins. In vitro, human neutrophil peptides 1 to 3 were not able to kill the bacilli even at much higher levels. These studies support the concept that human neutrophils are directly involved in defense against infection with M. tuberculosis.

* Corresponding author. Mailing address: Department of Immunology, National Jewish Medical and Research Center, and University of Colorado Health Sciences Center, 1400 Jackson St., Denver, CO 80206. Phone: (303) 398-1623. Fax: (303) 398-1225. E-mail: kisichk{at}njc.org.

Editor: S. H. E. Kaufmann

Infection and Immunity, August 2002, p. 4591-4599, Vol. 70, No. 8
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.8.4591-4599.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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