Spatial and temporal regulation of neutrophil-attractant CXCL5/LIX in acute streptococcal pneumonia

Successful host defense against numerous pulmonary infections depends on bacterial clearance by polymorphonuclear leukocytes (PMNs). However, excessive PMN-mediated inflammation can result in life-threatening lung injury.

Binding of chemokines with the ELR motif, including CXCL1/KC, CXCL2/MIP-2 and CXCL5/LIX, is one mechanism that initiates PMN access to sites of infection. Previously, we described that absence of epithelial-derived CXCL5/LIX, followed by impaired PMN recruitment, protects mice from fatal chronic Mycobacterium tuberculosis infection. Now, we aim at deciphering the role murine CXCL5/LIX and its human orthologues CXCL5/ENA-78 and GCP-2/CXCL6 play in acute pulmonary Streptococcus pneumoniae (S. pn.) infection.

Analog to mycobacterial infection, CXCL5 in acute bacterial pneumonia shows a distinct spatial and temporal regulation. Amongst lung resident cells, epithelial cells are capable to secrete CXCL5/LIX or its orthologues following in vitro streptococcal infection, while alveolar macrophages do not secrete these chemokines in mice and men. Responsible for the induction of CXCL5 secretion is TLR2 engagement by streptococcal lipoproteins, but not lipoteichoid acid (LTA). It remains elusive whether absence of CXCL5 has relevant impact on streptococcal pneumonia.