A complex interplay between the extracellular matrix and the innate immune response to microbial pathogens

Abstract

The role of the host extracellular matrix (ECM) in infection tends to be neglected. However, the complex interactions between invading pathogens, host tissues and immune cells occur in the context of the ECM. On the pathogen side, a variety of surface and secreted molecules, including microbial surface components recognizing adhesive matrix molecules and tissue-degrading enzymes, are employed that interact with different ECM proteins to effectively establish an infection at specific sites. Microbial pathogens can also hijack or misuse host proteolytic systems to modify the ECM, evade immune responses or process biologically active molecules such as cell surface receptors and cytokines that direct cell behaviour and immune defence. On the host side, the ECM composition and three-dimensional ultrastructure undergo significant modifications, which have a profound impact on the specific signals that the ECM conveys to immune cells at the forefront of infection. Unexpectedly, activated immune cells participate in the remodelling of the local ECM by synthesizing ECM glycoproteins, proteoglycans and collagen molecules. The close interplay between the ECM and the innate immune response to microbial pathogens ultimately affects the outcome of infection. This review explores and discusses recent data that implicate an active role for the ECM in the immune response to infection, encompassing antimicrobial activities, microbial recognition, macrophage activation, phagocytosis, leucocyte population balance, and transcriptional and post-transcriptional regulation of inflammatory networks, and may foster novel antimicrobial approaches.

Oligomeric amyloid beta prevents myelination in a clusterin-dependent manner

“…In addition to Lumican, multiple other proteins involved in extracellular matrix organization, a role already attributed to OPCs, are particularly enriched in this cluster [68][69][70] . Intriguingly, Lumican is known to be involved in the recruitment of immune cells and the regulation of cellular infiltration of tissue [71][72][73][74] . This cluster showed significant upregulation of genes related to cytokine mediated signaling, consistent with recent papers indicating that OPCs may be playing an active role in regulating the immune system, interrogating the function and transcriptional signature of this cluster of OPCs may further elucidate how OPCs may be interacting with the immune system and modulating the CNS environment to affect neuronal behavior and function 16,17,20,63 .…”

Eclectic characterisation of chemically modified cell-derived matrices obtained by metabolic glycoengineering and re-assessment of commonly used methods

“…29 Furthermore, and in direct comparison to collagen type I as a representative of a typical ECM-specic component, natural ECM consists of up to 300 different proteins in tissue-specic combinations and concentrations in a broad range of molecular weights also leading to additional less dened bands. 30,31 The intensely stained gel pockets in the upper part of the gel suggest that there are also ECM components present, which are too large to penetrate the small-pored acrylamide gel. Another quite likely explanation for this effect could be that covalently cross-linked macromolecular complexes were present in the (click)ECM samples which is very likely as almost all main components of the ECM are known to exhibit peptide sequences that contribute to the cross-linking of the matrix.…”

“…Deciding which conversion factor is the most appropriate one is not trivial as ECM is known to be a highly complex and dynamic mixture of biomolecules composed of up to 300 different proteins in tissue-specic combinations and concentrations. 30 Since the exact composition of the (click)ECM investigated in this study is not itemised in such detail, it is possibly not feasible to choose one specic factor. In fact, we suggest considering a tissue-specic range.…”

Characterization of Matrix Metalloprotease-9 Gene from Nile tilapia (Oreochromis niloticus) and Its High-Level Expression Induced by the Streptococcus agalactiae Challenge

“…MMP-9 has an immuno-regulatory function in mice cornea against Pseudomonas aeruginosa by proteolysis and upregulating cytokines/chemokines [43]. Furthermore, during the pulmonary infection of mice by Francisella tularensis, MMP-9 can generate proinflammatory ECM-derived peptides against the infection [44]. Similarly, Ciona MMP-9 is involved in inflammatory responses induced by a lipopolysaccharide based on the elevated mRNA levels and enzymatic activity of MMP-9 [3].…”