The Role of Innate Leukocytes during Influenza Virus Infection

Abstract

Influenza virus infection is a serious threat to humans and animals, with the potential to cause severe pneumonia and death. Annual vaccination strategies are a mainstay to prevent complications related to influenza. However, protection from the emerging subtypes of influenza A viruses (IAV) even in vaccinated individuals is challenging. Innate immune cells are the first cells to respond to IAV infection in the respiratory tract. Virus replication-induced production of cytokines from airway epithelium recruits innate immune cells to the site of infection. These leukocytes, namely, neutrophils, monocytes, macrophages, dendritic cells, eosinophils, natural killer cells, innate lymphoid cells, and γδ T cells, become activated in response to IAV, to contain the virus and protect the airway epithelium while triggering the adaptive arm of the immune system. This review addresses different anti-influenza virus schemes of innate immune cells and how these cells fine-tune the balance between immunoprotection and immunopathology during IAV infection. Detailed understanding on how these innate responders execute anti-influenza activity will help to identify novel therapeutic targets to halt IAV replication and associated immunopathology.

Respiratory Barrier as a Safeguard and Regulator of Defense Against Influenza A Virus and Streptococcus pneumoniae

“…The respiratory mucosal barrier contains sentinel cells comprised of AMs, dendritic cells (DCs), γδ T-cells, and innate lymphoid cells (ILCs) which support the antiviral immune response at early and late phases of IAV infection as recently reviewed by us (46). While functional responses in each of these cells during influenza has been investigated, their interactions with the epithelium during an ongoing infection is not fully explored.…”

Diverse and Unexpected Roles of Human Monocytes/Macrophages in the Immune Response to Influenza Virus

“…Monocytes and macrophages are central to the development as well as expression of the human immune response and its defense against influenza A virus (IAV) infection. Such cells are resident in the respiratory tract [1][2][3][4], and additional monocytes/macrophages are rapidly and vigorously recruited to the respiratory tract upon virus challenge [3][4][5]. Those recruited cells are susceptible to infection by IAV, as are co-recruited lymphocytes [6,7].…”

“…Monocytes/macrophages participate in both the expression of innate immunity and in the development of the adaptive immune response that is responsible for recovery from IAV infection. In the former role, they can be formidable producers of interferon [4,11] and other cytokines [10], for example. In the latter role, they have long been recognized as important accessory cells for antigen presentation and activation of lymphocytes in response to the challenge [1,12,13].…”

Abnormal immunity of non-survivors with COVID-19: predictors for mortality

“…It has been reported that neutrophilia and lymphocytopenia were signi cantly associated with higher risks of the development of ARDS [5]. Also, it has been showed that phagocytosis, release of granular contents, and secrection of cytokines are important effector functions of stimulated neutrophils, suggesting a protective immunity against the virus [15] . However, excessive elevated neutrophils can lead to cytokine storm and tissue damage, resulting in severe pneumonia and death [15] , which have been found in patients with SARS [16,17] and MERS [18] .…”