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Infection and Immunity, March 2005, p. 1744-1753, Vol. 73, No. 3
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.3.1744-1753.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Neutrophil Responses to Mycobacterium tuberculosis Infection in Genetically Susceptible and Resistant Mice

Evgenyi B. Eruslanov,1 Irina V. Lyadova,1 Tatiana K. Kondratieva,1 Konstantin B. Majorov,1 Ilya V. Scheglov,1 Marianna O. Orlova,1 and Alexander S. Apt1*

Laboratory for Immunogenetics, Central Institute for Tuberculosis, Moscow, Russia1

Received 1 June 2004/ Returned for modification 17 August 2004/ Accepted 27 September 2004

The role of neutrophils in tuberculosis (TB) resistance and pathology is poorly understood. Neutrophil reactions are meant to target the offending pathogen but may lead to destruction of the host lung tissue, making the defending cells an enemy. Here, we show that mice of the I/St strain which are genetically susceptible to TB show an unusually high and prolonged neutrophil accumulation in their lungs after intratracheal infection. Compared to neutrophils from more resistant A/Sn mice, I/St neutrophils display an increased mobility and tissue influx, prolonged lifespan, low expression of the CD95 (Fas) apoptotic receptor, relative resistance to apoptosis, and an increased phagocytic capacity for mycobacteria. Segregation genetic analysis in (I/St x A/Sn)F2 hybrids indicates that the alleles of I/St origin at the chromosome 3 and 17 quantitative trait loci which are involved in the control of TB severity also determine a high level of neutrophil influx. These features, along with the poor ability of neutrophils to restrict mycobacterial growth compared to that of lung macrophages, indicate that the prevalence of neutrophils in TB inflammation contributes to the development of pathology, rather than protection of the host, and that neutrophils may play the role of a "Trojan horse" for mycobacteria.

* Corresponding author. Mailing address: Laboratory for Immunogenetics, Central Institute for Tuberculosis, Yauza Alley 2, Moscow 107564, Russia. Phone: (7095) 268 78 10. Fax: (7095) 963 80 00. E-mail: asapt{at}aha.ru.

Editor: A. D. O'Brien

Infection and Immunity, March 2005, p. 1744-1753, Vol. 73, No. 3
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.3.1744-1753.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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