Complex Roles of Neutrophils during Arboviral Infections

Abstract

Arboviruses are known to cause large-scale epidemics in many parts of the world. These arthropod-borne viruses are a large group consisting of viruses from a wide range of families. The ability of their vector to enhance viral pathogenesis and transmission makes the development of treatments against these viruses challenging. Neutrophils are generally the first leukocytes to be recruited to a site of infection, playing a major role in regulating inflammation and, as a result, viral replication and dissemination. However, the underlying mechanisms through which neutrophils control the progression of inflammation and disease remain to be fully understood. In this review, we highlight the major findings from recent years regarding the role of neutrophils during arboviral infections. We discuss the complex nature of neutrophils in mediating not only protection, but also augmenting disease pathology. Better understanding of neutrophil pathways involved in effective protection against arboviral infections can help identify potential targets for therapeutics.

Neutrophils in COVID-19: Not Innocent Bystanders

“…Although neutrophils express the L-SIGN and DC-SIGN C-type lectins receptors that have been suggested to act as entry receptors for SARS-CoV-2, there is conflicting evidence about active infection of neutrophils with the virus. In other ssRNA viruses such as West Nile and influenza virus neutrophils serve as an important viral reservoir and contain actively replicating virus, and studies with human immunodeficiency virus (HIV) and Respiratory syncytial virus (RSV) viral models suggest that neutrophils can internalise virus without productive infection ( 66 ). Neutrophils are important for viral detection and initiation of downstream effector immune pathways but the replicative ability of ssRNA virus SARS-CoV-2 within neutrophils is not known.…”

Neutrophil Recruitment and Participation in Severe Diseases Caused by Flavivirus Infection

“…Type-I IFNs act in an autocrine and paracrine way, binding to the type-I IFN receptor IFNAR and upregulating the expression of interferon stimulated genes (ISG) that culminate in an antiviral state incompatible with viral replication and dissemination. Thus, a transient or partial inhibition of interferon responses is a prerequisite for viral replication and the establishment of infection [ 39 , 40 , 41 ]. Viruses have evolved several molecular mechanisms to evade the host’s IFN responses including the inhibition of signaling pathways, ISG function and direct antagonism of type-I IFNs.…”

“…Neutrophils are able to internalize viruses bound to antibodies or opsonized by complement, and express PRRs such as TLR7, TLR8 and MDA5 that would be activated upon binding of viral genomes, depending on genome composition and structure [ 41 ]. Neutrophils are not target cells in the majority of viral infections, being either impervious to infection or nonpermissive of viral replication [ 29 , 43 ].…”

Annexin A1-FPR2/ALX Signaling Axis Regulates Acute Inflammation during Chikungunya Virus Infection

“…At the same time, innate immune cells such as neutrophils and monocytes are recruited to the infection site [ 5 , 6 ]. Neutrophils produce reactive oxygen species (ROS) and neutrophil extracellular traps (NET) which contribute to a process of controlling CHIKV acute infection [ 7 , 8 ]. However, persistent inflammation can lead to the chronic phase of CF with the development of incapacitating rheumatic disorders [ 9 , 10 ].…”