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Infectious disease, the innate immune response, and fibrosis
Alessia Meneghin, Cory M. Hogaboam
Alessia Meneghin, Cory M. Hogaboam
Published March 1, 2007
Citation Information: J Clin Invest. 2007;117(3):530-538. https://doi.org/10.1172/JCI30595.
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Review Series

Infectious disease, the innate immune response, and fibrosis

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Abstract

The unrelenting and destructive progression of most fibrotic responses in the pulmonary, cardiovascular, integumentary, and alimentary systems remains a major medical challenge for which therapies are desperately needed. The pathophysiology of fibrosis remains an enigma, but considerable research and debate surrounds the question of whether chronic inflammation is the key driver of unrestrained wound healing (i.e., the fibrotic response) in these and other organ systems. This Review describes how infectious pathogens, chronic inflammation, and unrestrained fibroproliferation are likely to be part of a dynamic, unrelenting process propelling human fibrotic diseases.

Authors

Alessia Meneghin, Cory M. Hogaboam

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Figure 1

Persistent infectious stimuli initiate and sustain the fibrotic process.

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Persistent infectious stimuli initiate and sustain the fibrotic process....
Pathogens such as bacteria, viruses, fungi, and multicellular parasites represent major tissue injurious signals. The host response, mediated by the innate immune system, is intricately directed toward recognizing PAMPs through a myriad of PRRs. The concerted inflammatory and immune efforts of several immune and nonimmune cell types, including (but not limited to) classically activated macrophages (M1 macrophages), T cells, eosinophils, B cells, DCs, neutrophils, epithelial cells, and fibroblasts, contribute to the chronic inflammatory response. A dominant Th1 cytokine response normally characterizes an effective immune response against most pathogens, except most multicellular and extracellular parasites. Should pathogens and their byproducts be effectively cleared, the affected tissue often heals appropriately and the inflammatory process resolves. However, pathogens use various survival strategies to avoid elimination, and this leads to their persistence or the persistence of their byproducts in the host. The cytokine pattern associated with the ineffective response is often skewed toward the Th2 cytokine pattern. The resulting fibrotic response might be a consequence of the actions of unique cells such as the ECM component–synthesizing myofibroblast and the alternatively activated macrophage (M2 macrophage). The fibrotic response, in turn, might facilitate the persistence of pathogens and their byproducts, thereby allowing this vicious cycle to continue.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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