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    Rhinoviruses facilitate secondary bacterial infections by targeting a new important player in phagocytosis, Arpin

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    A study performed by the team F. Niedergang

    The team at Florence Niedergang  shows that human rhinoviruses, which cause colds, are able to reduce the ability of macrophages to capture respiratory bacteria,

    which can then develop as opportunistic bacteria. For this, rhinoviruses target the Arpin protein, whose major role in phagocytosis is revealed here by these viruses! This study, performed in collaboration with Pierre-Régis Burgel (AP-HP Cochin Hospital and Institut Cochin) and researchers from AstraZeneca (Sweden), has just been published in the journal EMBO reports.

     

    Human rhinoviruses are viruses of the Picornaviridae family that infect the upper airways and usually cause benign infections, mostly colds. However, for patients with chronic inflammatory diseases such as Chronic Obstructive Pulmonary Disease (COPD) or asthma, these viral infections exacerbate symptoms and frequently lead to bacterial superinfections.

    Macrophages play a major role in innate immunity, airway monitoring and local debris removal. In COPD, alveolar macrophages are in greater numbers, but less able to remove debris and bacteria, and this lack of bacterial clearance is exacerbated by rhinovirus infection. The mechanisms responsible for these macrophage defects are not well known.

    Researchers have shown that the infection of macrophages by human rhinovirus type 16 leads to a strong decrease in their ability to internalize various bacteria such as non-typeable Haemophilus influenzae, S. aureusP. aeruginosa, or various opsonized particles. Polymerization of the actin cytoskeleton is the driving force that can deform the plasma membrane and initiate phagocytosis. When macrophages are infected by rhinoviruses, this process is initiated but internalization does not take place efficiently. The virus induces a lower expression of a protein that inhibits actin polymerization (Arpin), which essential role in phagocytosis is revealed here.

    Thus, when a decrease in expression of the Arpin protein is induced by RNA interference, the phagocytosis efficiency is also greatly reduced. Experiments with rhinovirus infection and complementation with ectopic expression of the protein demonstrate that Arpin is the target cell factor for the virus to block phagocytosis.

    The authors reveal in this study the first cellular factor targeted by rhinovirus 16, which explains the defects in phagocytosis and bacterial capture by macrophages under conditions of infections by these viruses.

     

    Figure: Arpin, a negative regulator of the Arp2 / 3 complex plays a key role in the formation of phagosomes. Its expression is diminished in macrophages treated with human rhinovirus, which explains defects in phagocytosis and in bacterial capture.

    In perspective, this study identifies a new target to develop strategies for restoring the phagocytosis and bacterial clearance functions of airway macrophages.

     

    Reference

    Arpin is critical for phagocytosis in macrophages and is targeted by human rhinovirus. Jubrail J, Africano-Gomez K, Herit F, Mularski A, Bourdoncle P, Oberg L, Israelsson E, Burgel PR, Mayer G, Cunoosamy DM, Kurian N, Niedergang F.  EMBO Rep. 2019, Nov 13:e47963.

     

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