Cigarette smoking can manipulate signalling molecules to subvert macrophage functions, hindering the innate immune response against pneumococcal infection and promoting infectivity, according to new trial results published in the Journal of Microbiology, Immunology, and Infection.
By Like Halpern
Key Takeaways
- Cigarette smoking impairs macrophage function, reducing innate immune response against pneumococcal infection and increasing infection susceptibility.
- Smokers have more potential pathogens in their nasopharyngeal flora, leading to increased bacterial colonization and lung inflammation.
One of the leading causes of mortality worldwide, cigarette smoke (CS) inhalation can lead to acute lung and respiratory tract inflammation. This is associated with bacterial colonization; when bacteria such as pneumococcus enter the respiratory tract, bacterial colonization can occur. Smokers have more potential pathogens in their nasopharyngeal flora than non-smokers.
In vivo models have demonstrated that pneumococcal infection and exposure to CS can synergistically aggravate lung damage. Streptococcus pneumoniae infection was observed to induce lung damage and alter microbiota composition for a longer time compared to control groups infected, but not exposed to CS. Despite these indications, the mechanisms behind CS-induced pulmonary inflammation in response to bacterial infection have yet to be examined.
The investigators sought to analyze whether CS can manipulate innate immune signalling against pneumococcal infection. Cell-based models with CS-exposed murine macrophages were established and then challenged with pneumococci to examine bacterial clearance and innate responses to infection.
First, the effects of cigarette smoke extract (CSE) on pneumococcal internalization by macrophages were examined. Results indicated that, compared with the mock treatment utilized as a comparison, 5% CSE exposure suppressed phagocytosis by macrophages; macrophage internalization of pneumococci was found to be significantly reduced upon 5% CSE treatment.
Differential cytokine production in macrophages was then identified. Co-treatment of CSE and pneumococci with a cytokine array led to the production of several cytokines in macrophages, with the secretion of CCL2, CCL4, CCL3, CXCL2, and CXCL-10 in pneumococcus-infected cells reduced due to CSE treatment.
The mRNA levels of these cytokines were subsequently assessed; the study authors found that the mRNA levels were increased in the pneumococcal-infected group compared with the mock group, but that mRNA levels were considerably decreased following CSE exposure.
Toll-like receptor 2 (TLR2) and nucleotide-binding oligomerization domain 2 (NOD2) signalling are involved in pneumococcus-induced cytokine production in innate cells. The investigators found that TLR2 and NOD2 levels were reduced in CSE-treated macrophages challenged with pneumococci, suggesting that CSE hampers the innate ability of macrophages to recognize pneumococci.
Macrophages, which act as innate immune cells and are essential in defending the body against microbial infections, can often be overcome by pathogens by inducing macrophage subversion, reducing pulmonary immune response and exacerbating microbial infectivity. Thus, smoking cigarettes constitutes a substantial risk for respiratory tract hyper-responsiveness and pathogen infections.
The present trial, according to the investigators, has established a reliable CSE-exposed macrophage cell model while thoroughly investigating the potential mechanisms of how CSE affects macrophage functions in response to pneumococcal infection. However, they caution that the in vitro model established in the trial may not fully reflect host pathophysiology.
“Understanding the mechanism of how CS affects macrophage functions may help in the identification of new methods for restoring cellular function in patients with pneumococcal infection,” the investigators concluded.
