TY - JOUR
T1 - Airway Epithelial Innate Immunity
AU - Johnston, Sebastian L.
AU - Goldblatt, David L.
AU - Evans, Scott E.
AU - Tuvim, Michael J.
AU - Dickey, Burton F.
N1 - Funding Information:
SJ was the National Institute for Health Research (NIHR) Emeritus Senior Investigator and receives support from the Asthma UK Clinical Chair (Grant CH11SJ), European Research Council Advanced Grant 788575 and the NIHR Imperial Biomedical Research Centre (BRC). DG was funded as a Howard Hughes Medical Institute medical research fellow. SE was funded by NIH grant R35 HL144805. MT and BD were funded by NIH grant R01 HL129795 and Cystic Fibrosis Foundation grants 18G0 and 19P0.
Publisher Copyright:
Copyright © 2021 Johnston, Goldblatt, Evans, Tuvim and Dickey.
PY - 2021/11/26
Y1 - 2021/11/26
N2 - Besides providing an essential protective barrier, airway epithelial cells directly sense pathogens and respond defensively. This is a frontline component of the innate immune system with specificity for different pathogen classes. It occurs in the context of numerous interactions with leukocytes, but here we focus on intrinsic epithelial mechanisms. Type 1 immune responses are directed primarily at intracellular pathogens, particularly viruses. Prominent stimuli include microbial nucleic acids and interferons released from neighboring epithelial cells. Epithelial responses revolve around changes in the expression of interferon-sensitive genes (ISGs) that interfere with viral replication, as well as the further induction of interferons that signal in autocrine and paracrine manners. Type 2 immune responses are directed primarily at helminths and fungi. Prominent pathogen stimuli include proteases and chitin, and important responses include mucin hypersecretion and chitinase release. Type 3 immune responses are directed primarily at extracellular microbial pathogens, including bacteria and fungi, as well as viruses during their extracellular phase of infection. Prominent microbial stimuli include bacterial wall components, such as lipopeptides and endotoxin, as well as microbial nucleic acids. Key responses are the release of reactive oxygen species (ROS) and antimicrobial peptides (AMPs). For all three types of response, paracrine signaling to neighboring epithelial cells induces resistance to infection over a wide field. Often, the epithelial effector molecules themselves also have signaling properties, in addition to the release of inflammatory cytokines that boost local innate immunity. Together, these epithelial mechanisms provide a powerful first line of pathogen defense, recruit leukocytes, and instruct adaptive immune responses.
AB - Besides providing an essential protective barrier, airway epithelial cells directly sense pathogens and respond defensively. This is a frontline component of the innate immune system with specificity for different pathogen classes. It occurs in the context of numerous interactions with leukocytes, but here we focus on intrinsic epithelial mechanisms. Type 1 immune responses are directed primarily at intracellular pathogens, particularly viruses. Prominent stimuli include microbial nucleic acids and interferons released from neighboring epithelial cells. Epithelial responses revolve around changes in the expression of interferon-sensitive genes (ISGs) that interfere with viral replication, as well as the further induction of interferons that signal in autocrine and paracrine manners. Type 2 immune responses are directed primarily at helminths and fungi. Prominent pathogen stimuli include proteases and chitin, and important responses include mucin hypersecretion and chitinase release. Type 3 immune responses are directed primarily at extracellular microbial pathogens, including bacteria and fungi, as well as viruses during their extracellular phase of infection. Prominent microbial stimuli include bacterial wall components, such as lipopeptides and endotoxin, as well as microbial nucleic acids. Key responses are the release of reactive oxygen species (ROS) and antimicrobial peptides (AMPs). For all three types of response, paracrine signaling to neighboring epithelial cells induces resistance to infection over a wide field. Often, the epithelial effector molecules themselves also have signaling properties, in addition to the release of inflammatory cytokines that boost local innate immunity. Together, these epithelial mechanisms provide a powerful first line of pathogen defense, recruit leukocytes, and instruct adaptive immune responses.
KW - airway
KW - epithelium
KW - immunity
KW - innate immunity
KW - mucus
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U2 - 10.3389/fphys.2021.749077
DO - 10.3389/fphys.2021.749077
M3 - Article
C2 - 34899381
AN - SCOPUS:85120955631
SN - 1664-042X
VL - 12
JO - Frontiers in Physiology
JF - Frontiers in Physiology
M1 - 749077
ER -