Lethal Influenza Infection: Is a Macrophage to Blame?

Overview

Journal Expert Rev Anti Infect Ther

Specialty Infectious Diseases

Date 2015 Sep 29

PMID 26414622

Citations 12

Authors

E Scott Halstead

Zissis C Chroneos

Affiliations

Soon will be listed here.

Abstract

Alveolar macrophages (AMs) are critical for immunity against influenza A virus (IAV) infection. Depletion, hyporeactivity, and disruption of AM development and differentiation are all associated with lethal IAV infection. AMs drive the innate immune response that limits IAV infection. AMs are crucial for steady-state homeostasis of pulmonary surfactant, and in turn surfactant proteins regulate AMs and participate in host defense against IAV. Known factors that are necessary for AM function and differentiation in vivo include surfactant proteins, the growth factor GM-CSF, the hormone receptor PPARγ, and the transcription factors PU.1 and Bach2. Although PU.1 and PPARγ are downstream effectors of GM-CSF, Bach2 works independently. GM-CSF and Bach2-deficient AMs have phenotypes with immature or alternatively activated states of differentiation, respectively, and both extremes are unsuitable for surfactant homeostasis. The activation state of AMs and the local microenvironment may determine the development of symptomatic versus asymptomatic IAV infection in different individuals.

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