Differential Ability of Pandemic and Seasonal H1N1 Influenza A Viruses To Alter the Function of Human Neutrophils

Abstract

Neutrophils are essential cells of host innate immunity. Although the role of neutrophils in defense against bacterial and fungal infections is well characterized, there is a relative paucity of information about their role against viral infections. Influenza A virus (IAV) infection can be associated with secondary bacterial coinfection, and it has long been posited that the ability of IAV to alter normal neutrophil function predisposes individuals to secondary bacterial infections. To better understand this phenomenon, we evaluated the interaction of pandemic or seasonal H1N1 IAV with human neutrophils isolated from healthy persons. These viruses were ingested by human neutrophils and elicited changes in neutrophil gene expression that are consistent with an interferon-mediated immune response. The viability of neutrophils following coculture with either pandemic or seasonal H1N1 IAV was similar for up to 18 h of culture. Notably, neutrophil exposure to seasonal (but not pandemic) IAV primed these leukocytes for enhanced functions, including production of reactive oxygen species and bactericidal activity. Taken together, our results are at variance with the universal idea that IAV impairs neutrophil function directly to predispose individuals to secondary bacterial infections. Rather, we suggest that some strains of IAV prime neutrophils for enhanced bacterial clearance. A long-standing notion is that IAV inhibits normal neutrophil function and thereby predisposes individuals to secondary bacterial infections. Here we report that seasonal H1N1 IAV primes human neutrophils for enhanced killing of. Moreover, we provide a comprehensive view of the changes in neutrophil gene expression during interaction with seasonal or pandemic IAV and report how these changes relate to functions such as bactericidal activity. This study expands our knowledge of IAV interactions with human neutrophils.

Neutrophils Induce a Novel Chemokine Receptors Repertoire During Influenza Pneumonia

“…Influenza infection has also shown to impair NADPH oxidase activity (Sun and Metzger, 2014). A study has shown that seasonal and pandemic influenza viruses differentially regulate neutrophil respiratory burst and phagocytosis (Malachowa et al, 2018). The ability of influenza virus to impair phagocytic function may be due to the inhibition of azurophilic granules with the lysosomes during phagocytosis, thus preventing bacterial killing (Abramson et al, 1982).…”

Comprehensive Transcriptomic Analysis Identifies Novel Antiviral Factors Against Influenza A Virus Infection

“…Phagocytes containing monocytes, macrophages, dendritic cells, and neutrophils are critical in the recognition, engulfment, and destruction of invading pathogens. To uncover the antiviral activities of phagocytes against different subtypes of influenza viruses, the transcriptome analysis of gene expression profiles was performed in human phagocytic cells (PBMC, monocytes, macrophages, pDC, and neutrophils) that were infected with different subtypes of influenza viruses, including H1N1, H5N1, and H7N7 (Table 5) (24,27,(35)(36)(37)(38)(39)(40)(41). Following the criteria of P<0.05 and |logFC|≥1.5, 12 genes (C19orf66, IL6, HESX1, IFNB1, IFITM3, ISG20, ISG15, HERC5, IFIT1, CCL8, IFIT2, and CXCL10) were overlapped and upregulated in H1N1-infected monocyte-derived macrophages and primary alveolar macrophages (Figure 7A).…”

The Role of Innate Leukocytes during Influenza Virus Infection

“…Furthermore, proinflammatory cytokines produced by neutrophils limit virus replication and halt progression to severe disease [43, 44] (Figure 1). Neutrophils are susceptible to IAV infection [45–47], although infection has been demonstrated to be both productive (for pH1N1) [48] and abortive (for seasonal H1N1 and WSN33) [45, 49]. These discrepancies might be related to virus subtypes/strains used.…”

“…Interestingly, mice treated with β -defensin had reduced IAV burden and an associated reduction in neutrophils in the lungs [21], underscoring the importance of a prudently adjudicated immune response to host protection. Nonetheless, IAV-infected neutrophils upregulate IFNs and other antiviral factors [45, 46] that limit viral replication (Figure 1).…”