Sustained desensitization to bacterial Toll-like receptor ligands after resolution of respiratory influenza infection

Didierlaurent, A, et al. J. Exp. Med. 205, 323-9 (2008)

Speaker: Wei-Cheng Huang (黃偉誠)          Time: 15:00~16:00, May. 14, 2008

Commentator: Dr. Yao Chang (張 堯博士)     Place: Room 601

Abstract:

In clinic, patients with lower respiratory tract infections are usually complicated with and die from secondary infections caused by unrelated pathogens¹. From epidemiological and animal studies, there is also evidence showing that after one respiratory tract infection, the host immunity is modified toward either the beneficial or detrimental role to successive infections², yet the mechanisms that underlying this phenomenon is still unknown. In this study, the authors demonstrated this effect was due to the alteration in innate immune system after recovered from respiratory tract infections. After resolution of an influenza infection, mice challenged with agonists of Toll-like receptors showed impaired neutrophil recruitment to the airway of mice, and this effect was evident and last for over 6 months. Similar responses were also observed in mice challenged with various bacteria. The defect in neutrophil recruitment was mediated by the decreased chemokine productions from desensitized alveolar macrophages. Although the levels of Toll-like receptor expression were not altered, the chemokine transcription was reduced and resulted from impaired NF-κBactivation drownstream TLR signaling in post-influenza alveolar macrophages. The decreased inflammation may be beneficial in reducing overall immunopathology but it suggested that the heightened bacterial loads due to the impaired clearance of bacteria could make mice vulnerable to secondary infections. In summary, this is the first report demonstrated that modified lung immunity was regulated by alveolar macrophages with sustained desensitization to TLRs ligands. Most importantly, this study provides an explanation of increased susceptibility to bacterial pneumonia followed after influenza infection.

References:

1.         Brundage, J.F. Interactions between influenza and bacterial respiratory pathogens: implications for pandemic preparedness. Lancet Infect Dis 6, 303-312 (2006).

2.         Didierlaurent, A., Goulding, J. & Hussell, T. The impact of successive infections on the lung microenvironment. Immunology 122, 457-465 (2007).