Background: The exact role of neutrophils in the pathogenesis of TB is poorly understood. Recent evidence suggests that neutrophils are not simply scavenging phagocytes in Mycobacterium tuberculosis (Mtb) infection. Methods: Three different types of clinical specimens from patients with active pulmonary TB who underwent lung surgery were examined: sputum, BAL fluid, and cavity contents. Differential cell separation and quantification were performed for intracellular and extracellular bacteria, and bacterial length was measured using microscopy. Results: Neutrophils were more abundant than macrophages in sputum (86.6% ± 2.2% vs 8.4% ± 1.3%) and in BAL fluid (78.8% ± 5.8% vs 11.8% ± 4.1%). Inside the cavity, lymphocytes (41.3% ± 11.2%) were the most abundant cell type, followed by neutrophils (38.8% ± 9.4%) and macrophages (19.5% ± 7.5%). More intracellular bacilli were found in neutrophils than macrophages in sputum (67.6% ± 5.6% vs 25.2% ± 6.5%), in BAL fluid (65.1% ± 14.4% vs 28.3% ± 11.6%), and in cavities (61.8% ± 13.3% vs 23.9% ± 9.3%). The lengths of Mtb were shortest in cavities (1.9 ± 0.1 m m), followed by in sputum (2.9 ± 0.1 m m) and in BAL fluid (3.6 ± 0.2 m m). Conclusions: Our results show that neutrophils are the predominant cell types infected with Mtb in patients with TB and that these intracellular bacteria appear to replicate rapidly. These results are consistent with a role for neutrophils in providing a permissive site for a final burst of active replication of the bacilli prior to transmission.
Bibliographical noteFunding Information:
Funding/Support: This research was supported in part by the Intramural Research Program of the National Institutes of Health, National Institute of Allergy and Infectious Diseases ( Z01 AI000783-11 ), and in part by a grant from the Bill and Melinda Gates Foundation and the Wellcome Trust through the Grand Challenges in Global Health Initiative (C.E.B. and S.-N.C.) Grant No. 37882 (Douglas Young, Imperial College, Principal Investigator).
All Science Journal Classification (ASJC) codes
- Pulmonary and Respiratory Medicine
- Critical Care and Intensive Care Medicine
- Cardiology and Cardiovascular Medicine