A question of self‐preservation: immunopathology in influenza virus infection

Abstract

Influenza A viruses that circulate normally in the human population cause a debilitating, though generally transient, illness that is sometimes fatal, particularly in the elderly. Severe complications arising from pandemic influenza or the highly pathogenic avian H5N1 viruses are often associated with rapid, massive inflammatory cell infiltration, acute respiratory distress, reactive hemophagocytosis and multiple organ involvement. Histological and pathological indicators strongly suggest a key role for an excessive host response in mediating at least some of this pathology. Here, we review the current literature on how various effector arms of the immune system can act deleteriously to initiate or exacerbate pathological damage in this viral pneumonia. Generally, the same immunological factors mediating tissue damage during the anti‐influenza immune response are also critical for efficient elimination of virus, thereby posing a significant challenge in the design of harmless yet effective therapeutic strategies for tackling influenza virus.

Granzyme A expression reveals distinct cytolytic CTL subsets following influenza A virus infection

“…A very interesting recent report describes the ability of grzA to induce proinflammatory cytokine production [16]. Inflammatory cascades can have a deleterious impact during influenza infection [33] and as such CTL subsets with higher grzA levels may contribute to immunopathology rather than protection. These possibilities remain to be investigated.…”

Negative Regulation of Lung Inflammation and Immunopathology by TNF-α during Acute Influenza Infection

“…1,2 It is now well established that lung immunopathology is one of the main causes of influenzarelated morbidity and mortality. [3][4][5][6][7][8][9][10][11] Influenza viruses are negative-stranded, enveloped RNA viruses belonging to the family Orthomyxoviridae that preferentially infect and replicate in bronchial epithelial cells. 7 Both innate and adaptive immune responses are key players in the host defense against influenza.…”

“…7 Both innate and adaptive immune responses are key players in the host defense against influenza. 8,9,[12][13][14] Part of such host immune responses involves the production of antiviral and inflammatory cytokines and chemokines from infected airway epithelial cells and leukocytes, including interferon (IFN)-␣/␤, TNF-␣, IFN-␥, keratinocytederived chemokine (KC), monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein-1 (MIP-1)␣/␤, MIP-3␣, interferon-␥ inducible protein 10 (IP-10), and regulated on activation normal T-cell expressed and secreted (RANTES). 9,[15][16][17] Cytotoxic CD8 T cells play an important role in influenza viral clearance by lysing virus-infected cells, and effective viral clearance from the lung is usually achieved within 7 to 10 days after primary infection.…”

“…9,[15][16][17] Cytotoxic CD8 T cells play an important role in influenza viral clearance by lysing virus-infected cells, and effective viral clearance from the lung is usually achieved within 7 to 10 days after primary infection. 8,12,13 A strong CD4 T-helper response is believed to contribute to the generation of robust hu-moral responses, important for neutralization of the virus. 8,12,13 Although these host immune responses are critical to influenza viral clearance, they often cause undesired lung immunopathology, severe cases of which may also develop irreversible tissue injury and fibrotic remodeling.…”

“…8,12,13 A strong CD4 T-helper response is believed to contribute to the generation of robust hu-moral responses, important for neutralization of the virus. 8,12,13 Although these host immune responses are critical to influenza viral clearance, they often cause undesired lung immunopathology, severe cases of which may also develop irreversible tissue injury and fibrotic remodeling. 7-10,18 -20 Much of the immunoregulatory mechanisms of influenza immunopathology and tissue injury still remain to be understood.…”