A pathologic two‐way street: how innate immunity impacts lung fibrosis and fibrosis impacts lung immunity

Warheit-Niemi, Helen; Hult, Elissa M; Moore, Bethany B.

doi:10.1002/cti2.1065

Cited by 19 publications

(9 citation statements)

References 88 publications

(183 reference statements)

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“…While the exact cellular and molecular mechanisms that drive the development of IPF have not been fully elucidated, considerable progress has been made in this field and the involvement of many key cell types and signaling molecules have been identified thus far. Notable among these discoveries, has been the role of the immune system in disease progression (6). While extensive research has been devoted to understanding how changes in the immune response contributes to further fibrotic development, the effects of these alterations on critical responses to infection are unknown.…”

Section: Introductionmentioning

confidence: 99%

Fibrotic lung disease inhibits immune responses to staphylococcal pneumonia via impaired neutrophil and macrophage function

Warheit-Niemi¹,

Edwards²,

SenGupta³

et al. 2022

JCI Insight

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Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal disease characterized by collagen deposition within the lung interstitium. Bacterial infection is associated with increased morbidity and more rapid mortality in IPF patient populations and pathogens such as methicillin-resistant Staphylococcus aureus (MRSA) are commonly isolated from the lungs of hospitalized IPF patients. Despite this, the effects of fibrotic lung injury on critical immune responses to infection remain unknown. In the present study, we show that, like human IPF, fibrotic mice infected with MRSA exhibit increased morbidity and mortality compared to uninfected fibrotic mice. We determine that fibrosis confers a defect in MRSA clearance compared to non-fibrotic mice, resulting from blunted innate immune responses. We show that fibrosis inhibits neutrophil intracellular killing of MRSA through impaired neutrophil elastase (NE) release and oxidative radical production. Additionally, we demonstrate that lung macrophages from fibrotic mice have impaired phagocytosis of MRSA. Our study describes potentially novel impairments to antimicrobial responses upon the development of pulmonary fibrosis and our findings suggest a possible mechanism for why IPF patients are at greater risk of morbidity and mortality related to infection.

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Section: Introductionmentioning

confidence: 99%

Fibrotic lung disease inhibits immune responses to staphylococcal pneumonia via impaired neutrophil and macrophage function

Warheit-Niemi¹,

Edwards²,

SenGupta³

et al. 2022

JCI Insight

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“…However, there is emerging evidence that innate and adaptive immune processes may also contribute to pulmonary fibrogenesis. [23][24][25][26][27] Understanding the interface between immunologic dysfunction and known genetic risk variants may deepen the understanding of the complexity of IPF.…”

Section: Introductionmentioning

confidence: 99%

Genetic Risk Factors for Idiopathic Pulmonary Fibrosis: Insights into Immunopathogenesis

Michalski¹,

Schwartz²

2021

JIR

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“…The lung is made up of dozens of cell types and has evolved architecturally into a series of branching airways and alveoli to support an efficient permeable transfer of oxygen and carbon dioxide for the respiratory system and the whole body (Warheit-Niemi et al 2019 ). An appropriate function of the lung is predominantly dependent on the alveolar epithelial cells, one of the predominant cells in the respiratory tract (Fig.…”

Section: Respiratory Barrier Integritymentioning

confidence: 99%

Epithelial Dysfunction in Lung Diseases: Effects of Amino Acids and Potential Mechanisms

Chen

Jin

Yang

et al. 2020

Advances in Experimental Medicine and Biology

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Lung diseases affect millions of individuals all over the world. Various environmental factors, such as toxins, chemical pollutants, detergents, viruses, bacteria, microbial dysbiosis, and allergens, contribute to the development of respiratory disorders. Exposure to these factors activates stress responses in host cells and disrupt lung homeostasis, therefore leading to dysfunctional epithelial barriers. Despite significant advances in therapeutic treatments for lung diseases in the last two decades, novel interventional targets are imperative, considering the side effects and limited efficacy in patients treated with currently available drugs. Nutrients, such as amino acids (e.g., arginine, glutamine, glycine, proline, taurine, and tryptophan), peptides, and bioactive molecules, have attracted more and more attention due to their abilities to reduce oxidative stress, inhibit apoptosis, and regulate immune responses, thereby improving epithelial barriers. In this review, we summarize recent advances in amino acid metabolism in the lungs, as well as multifaceted functions of amino acids in attenuating inflammatory lung diseases based on data from studies with both human patients and animal models. The underlying mechanisms for the effects of physiological amino acids are likely complex and involve cell signaling, gene expression, and anti-oxidative reactions. The beneficial effects of amino acids are expected to improve the respiratory health and well-being of humans and other animals. Because viruses (e.g., coronavirus) and environmental pollutants (e.g., PM2.5 particles) induce severe damage to the lungs, it is important to determine whether dietary supplementation or intravenous administration of individual functional amino acids (e.g., arginine-HCl, citrulline, N-acetylcysteine, glutamine, glycine, proline and tryptophan) or their combinations to affected subjects may alleviate injury and dysfunction in this vital organ.

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A pathologic two‐way street: how innate immunity impacts lung fibrosis and fibrosis impacts lung immunity

Cited by 19 publications

References 88 publications

Fibrotic lung disease inhibits immune responses to staphylococcal pneumonia via impaired neutrophil and macrophage function

Fibrotic lung disease inhibits immune responses to staphylococcal pneumonia via impaired neutrophil and macrophage function

Genetic Risk Factors for Idiopathic Pulmonary Fibrosis: Insights into Immunopathogenesis

Epithelial Dysfunction in Lung Diseases: Effects of Amino Acids and Potential Mechanisms

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