Airway delivery of silica increases susceptibility to mycobacterial infection in mice: potential role of repopulating macrophages.
Silica exposure results in an increased lifelong risk of developing mycobacterial pulmonary infections. To date, there are no animal models that replicate this finding to permit assessment of the mechanisms underlying susceptibility to mycobacterial infection. To test the hypothesis that prior silica exposure increases risk of mycobacterial infection, we intratracheally (I.T.) administered silica, a control dust (Al(2)O(3)) or saline into mechanically ventilated C57BL/6 mice. Later, the mice received Mycobacterium avium or Mycobacterium tuberculosis I.T. Mice were sacrificed at defined time points and mycobacteria in lung homogenates were quantified. M. avium or M. tuberculosis infection was markedly increased in silica-exposed mice compared with mice exposed to either Al(2)O(3) or saline beginning 3 wk after silica exposure. Similarly, lung sections from silica-exposed mice had many more acid fast bacilli(+) (AFB(+)) organisms than from control mice. Alveolar macrophages (AMs) from bronchoalveolar lavage of silica-exposed mice also revealed a higher number of mycobacteria compared with mice treated with Al(2)O(3) or saline. In addition, passive transfer of AMs from silica-exposed mice to control mice increased M. tuberculosis susceptibility. These results indicate that silica exposure converts mycobacteria-resistant mice into mycobacteria-susceptible mice via a process that likely involves a new population of AMs that are more susceptible to mycobacterial infection.
Pasula
Rajamouli
R
Department of Internal Medicine, University of Cincinnati, Cincinnati, OH 45267, USA. pasular@ucmail.uc.edu
Britigan
Bradley E
BE
Turner
Joanne
J
Martin
William J
WJ
D000537:Aluminum Oxide / Q000009:adverse effects; D000818:Animals; D004198:Disease Susceptibility / Q000209:etiology*; D019570:Inhalation Exposure / Q000009:adverse effects; D016676:Macrophages, Alveolar / Q000382:microbiology*; D051379:Mice; D009164:Mycobacterium Infections / Q000139:chemically induced / Q000209:etiology*; D009162:Mycobacterium avium; D009169:Mycobacterium tuberculosis; D012137:Respiratory System; D012822:Silicon Dioxide / Q000008:administration & dosage / Q000009:adverse effects*
D012822:Silicon Dioxide; D000537:Aluminum Oxide