HRV16 Impairs Macrophages Cytokine Response to a Secondary Bacterial Trigger

Human rhinovirus is frequently seen as an upper respiratory tract infection but growing evidence proves the virus can cause lower respiratory tract infections in patients with chronic inflammatory lung diseases including chronic obstructive pulmonary disease (COPD). In addition to airway epithelial cells, macrophages are crucial for regulating inflammatory responses to viral infections. However, the response of macrophages to HRV has not been analyzed in detail. We used in vitro monocyte-derived human macrophages to study the cytokine secretion of macrophages in response to the virus. Our results showed that macrophages were competent at responding to HRV, as a robust cytokine response was detected. However, after subsequent exposure to non-typeable Haemophilus influenzae (NTHi) or to LPS, HRV-treated macrophages secreted reduced levels of pro-inflammatory or regulatory cytokines. This “paralyzed” phenotype was not mimicked if the macrophages were pre-treated with LPS or CpG instead of the virus. These results begin to deepen our understanding into why patients with COPD show HRV-induced exacerbations and why they mount a defective response toward NTHi

Macrophage phagocytosis cracking the defect code in COPD

In the normal non-diseased lung, various macrophage populations maintain homeostasis and sterility by ingesting and clearing inhaled particulates, pathogens and apoptotic cells from the local environment. This process of phagocytosis leads to the degradation of the internalized material, coordinated induction of gene expression, antigen presentation and cytokine production, implicating phagocytosis as a central regulator of innate immunity. Phagocytosis is extremely efficient and any perturbation of this function is deleterious. In inflammatory lung diseases such as chronic obstructive pulmonary disease (COPD), despite their increased numbers, macrophages demonstrate significantly reduced phagocytic capacity of bacteria and apoptotic cells. This defect could play a role in dysbiosis of the lung microbiome contributing to disease pathophysiology. In this review, we will discuss lung macrophages, describe phagocytosis and its related downstream processes and the reported phagocytosis defects in COPD. Finally, we will briefly examine current strategies that focus on restoring the phagocytic capabilities of lung macrophages that may have utility in COPD

HRV16 Impairs Macrophages Cytokine Response to a Secondary Bacterial Trigger

International audienc

Arpin is critical for phagocytosis in macrophages and is targeted by human rhinovirus

International audienc