Cigarette Smoke Exposure Impairs Pulmonary Bacterial Clearance and Alveolar Macrophage Complement-Mediated Phagocytosis of Streptococcus pneumoniae

Abstract

Cigarette smoke exposure increases the risk of pulmonary and invasive infections caused by Streptococcus pneumoniae, the most commonly isolated organism from patients with community-acquired pneumonia. Despite this association, the mechanisms by which cigarette smoke exposure diminishes host defense against S. pneumoniae infections are poorly understood. In this study, we compared the responses of BALB/c mice following an intratracheal challenge with S. pneumoniae after 5 weeks of exposure to room air or cigarette smoke in a whole-body exposure chamber in vivo and the effects of cigarette smoke on alveolar macrophage phagocytosis of S. pneumoniae in vitro. Bacterial burdens in cigarette smoke-exposed mice were increased at 24 and 48 h postinfection, and this was accompanied by a more pronounced clinical appearance of illness, hypothermia, and increased lung homogenate cytokines interleukin-1␤ (IL-1␤), IL-6, IL-10, and tumor necrosis factor alpha (TNF-␣). We also found greater numbers of neutrophils in bronchoalveolar lavage fluid recovered from cigarette smoke-exposed mice following a challenge with heat-killed S. pneumoniae. Interestingly, overnight culture of alveolar macrophages with 1% cigarette smoke extract, a level that did not affect alveolar macrophage viability, reduced complement-mediated phagocytosis of S. pneumoniae, while the ingestion of unopsonized bacteria or IgG-coated microspheres was not affected. This murine model provides robust additional support to the hypothesis that cigarette smoke exposure increases the risk of pneumococcal pneumonia and defines a novel cellular mechanism to help explain this immunosuppressive effect.

Pulmonary cytokine composition differs in the setting of alcohol use disorders and cigarette smoking

“…increased pulmonary bacterial burden, and worsened clinical signs of pneumococcal pneumonia (42). Our investigations suggest the possibility that cigarette smoke exposure results in a baseline increase in the proinflammatory state of the lung.…”

Cigarette Smoke Primes the Pulmonary Environment to IL-1α/CXCR-2–Dependent Nontypeable Haemophilus influenzae–Exacerbated Neutrophilia in Mice

“…Cigarette smoke exerts damaging and proinflammatory effects in the lungs but also can directly suppress innate and adaptive immune processes (7)(8)(9)(10). Studies in animal models have demonstrated that exposure to cigarette smoke exacerbates inflammatory responses elicited by several different bacterial agents, including nontypeable Haemophilus influenzae (NTHi), Pseudomonas aeruginosa, and Streptococcus pneumonia (11)(12)(13)(14). In all studies, the cellular composition of the bacteria-exacerbated inflammatory response was neutrophilic in nature.…”

Impact of cigarette smoke exposure on host–bacterial pathogen interactions

“…Smoke also seems to exacerbate the impairment in mucociliary clearance of S. pneumoniae induced by the ingestion of ethanol [94]. Cigarette smoke has been shown to prevent complement-mediated phagocytosis of S. pneumoniae by alveolar macrophages, while the ingestion of unopsonised bacteria or IgG-coated microspheres is not affected, thus impairing pulmonary bacterial clearance [95].…”