The monocyte-dependent immune response to bacterial infections is systemically suppressed in COPD

Rationale: Smokers and COPD patients are abnormally susceptible to bacterial infections, which exacerbate COPD. Targeting the causative molecular defects could reduce exacerbation rates. In response to bacterial airway infections, circulating monocytes enter the lung and contribute to infection defense by releasing cytokines. Hypothesis: Monocyte responses to pathogen-associated molecular patterns (PAMPs) of gram-positive bacteria are impaired in smokers/COPD. Methods: Pure peripheral blood monocytes of never-smokers (NS), smokers without (S) and with COPD (n=10/10/14) were stimulated in concentration-response experiments with gram-positive PAMPs (peptidoglycan, PGN; lipoteichoic acid, LTA; lipopeptide amiA) or S. aureus (SaE) or S. pneumoniae (SpE) extract. TNFα, GM-CSF, IL-8 and PAMP receptors (NOD2, TLR2) were measured by ELISA, qRT-PCR, Western Blot. Results: All PAMPs/extracts induced TNFα, GM-CSF and IL-8 but not NOD2 or TLR2. PGN/SaE/SpE-induced TNFα releases were reduced in S and COPD compared to NS, correlated positively to FEV1 but negatively to packyears (all p Discussion: The innate immune response to bacteria is suppressed by smoking and in COPD because monocyte cytokine responses to gram-positive PAMPs are impaired - possibly due to systemic NOD2 reduction. This might explain the increased susceptibility of S and COPD to bacterial infections. Targeting PAMP-associated signaling might reduce exacerbation rates.