Inhibition of CL-11 reduces pulmonary inflammation in a mouse model of Klebsiella pneumoniae lung infection

Abstract

Infection caused by K. pneumoniae is associated with severe inflammation due to stimulation of the innate immune components including the complement system, which is the main player of the innate immune response. Excessive complement-mediated inflammation may cause severe lung injury. Here we clearly show that K. pneumoniae binds to different lectin pathway carbohydrate recognition molecules and activates the complement cascade via the LP. Administration of anti-CL-11 antibodies 6 h before the infection impairs LP functional activity but it shows no effect on the survival time of mice infected with K. pneumoniae. Similarly, no significant difference in bacterial load in blood and lung tissues was observed between mice that received anti-CL-11 and control group treated with an isotype antibody. Interestingly, treatment of mice with anti-CL-11 prior to infection significantly improved histopathological changes and lung injury score induced by K. pneumoniae. Moreover, administration of anti-CL-11 reduced leukocytes infiltration into lung tissues and decreased the levels of the inflammatory mediators TNF-α, IL-6, and IL-1β in the infected mice. These findings indicate that inhibition of the LP could secure a significant level of protection against lung injury during the infection caused by K. pneumoniae.

Keywords: Acute lung injury; CL-11; IL-6; Klebsiella pneumoniae; Lectin pathway; TNF-α.