Identification of human cathelicidin peptide LL-37 as a ligand for macrophage integrin &amp;alpha;&lt;sub&gt;M&lt;/sub&gt;&amp;beta;&lt;sub&gt;2&lt;/sub&gt; (Mac-1, CD11b/CD18) that promotes phagocytosis by opsonizing bacteria

Lishko, Valeryi K.; Moreno, Benjamin; Podolnikova, Nataly P.; Ugarova, Tatiana P.

doi:10.2147/rrbc.s107070

Cited by 28 publications

(10 citation statements)

References 58 publications

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“…The inhibition of apoptosis in neutrophils was abrogated by blocking P2X7 and the PI3K pathway (102), while the chemoattractant function of cathelicidin was inhibited by both a specific FPR2 inhibitor and the G-protein coupled receptor inhibitor pertussis toxin (16). Moreover, LL-37 directly activated CD11b/CD18 to increase monocyte migration (103) and phagocytosis of LL-37 coated bacteria (104), indicating a role of cathelicidin in leukocyte phagocytosis and migration through CD11b/CD18. Indirect activation of CD11b/CD18 by LL-37 and CRAMP on monocytes can also occur through activation of FPR2 (105).…”

Section: Cathelicidinsmentioning

confidence: 99%

The Network of Colonic Host Defense Peptides as an Innate Immune Defense Against Enteropathogenic Bacteria

et al. 2020

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Host defense peptides, abundantly secreted by colonic epithelial cells and leukocytes, are proposed to be critical components of an innate immune response in the colon against enteropathogenic bacteria, including Shigella spp., Salmonella spp., Clostridium difficile, and attaching and effacing Escherichia coli and Citrobacter rodentium. These short cationic peptides are bactericidal against both Gram-positive and-negative enteric pathogens, but may also exert killing effects on intestinal luminal microbiota. Simultaneously, these peptides modulate numerous cellular responses crucial for gut defenses, including leukocyte chemotaxis and migration, wound healing, cytokine production, cell proliferation, and pathogen sensing. This review discusses recent advances in our understanding of expression, mechanisms of action and microbicidal and immunomodulatory functions of major colonic host defense peptides, namely cathelicidins, β-defensins, and members of the Regenerating islet-derived protein III (RegIII) and Resistin-like molecule (RELM) families. In a theoretical framework where these peptides work synergistically, aspects of pathogenesis of infectious colitis reviewed herein uncover roles of host defense peptides aimed to promote epithelial defenses and prevent pathogen colonization, mediated through a combination of direct antimicrobial function and fine-tuning of host immune response and inflammation. This interactive host defense peptide network may decode how the intestinal immune system functions to quickly clear infections, restore homeostasis and avoid damaging inflammation associated with pathogen persistence during infectious colitis. This information is of interest in development of host defense peptides (either alone or in combination with reduced doses of antibiotics) as antimicrobial and immunomodulatory therapeutics for controlling infectious colitis.

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Section: Cathelicidinsmentioning

confidence: 99%

The Network of Colonic Host Defense Peptides as an Innate Immune Defense Against Enteropathogenic Bacteria

et al. 2020

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“…Cathelicidins have multiple functions, including inducing antimicrobial action, guiding immune cell differentiation toward proinflammatory effects and steering chemotaxis (323). Cathelicidins opsonize bacteria to significantly enhance phagocytosis of S. aureus by macrophages in vitro by up to 10fold (324). Cathelicidin fowlcidin-1 induces expression of proinflammatory cytokines in order to activate macrophages protecting mice from death in a normally lethal intraperitoneal MRSA infection (325).…”

Section: Antimicrobial Peptides In Macrophage Defense Against S Aureusmentioning

confidence: 99%

The Role of Macrophages in Staphylococcus aureus Infection

et al. 2021

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Staphylococcus aureus is a member of the human commensal microflora that exists, apparently benignly, at multiple sites on the host. However, as an opportunist pathogen it can also cause a range of serious diseases. This requires an ability to circumvent the innate immune system to establish an infection. Professional phagocytes, primarily macrophages and neutrophils, are key innate immune cells which interact with S. aureus, acting as gatekeepers to contain and resolve infection. Recent studies have highlighted the important roles of macrophages during S. aureus infections, using a wide array of killing mechanisms. In defense, S. aureus has evolved multiple strategies to survive within, manipulate and escape from macrophages, allowing them to not only subvert but also exploit this key element of our immune system. Macrophage-S. aureus interactions are multifaceted and have direct roles in infection outcome. In depth understanding of these host-pathogen interactions may be useful for future therapeutic developments. This review examines macrophage interactions with S. aureus throughout all stages of infection, with special emphasis on mechanisms that determine infection outcome.

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“…While best known for their direct antimicrobial activity against a broad spectrum of bacteria (27)(28)(29), viruses (30)(31)(32), fungi (33,34), and parasites (35,36), it is now wellestablished that these peptides also have the potential to modulate immune responses in various ways. This includes regulation of neutrophil and monocyte chemotaxis (37)(38)(39), induction of chemokine expression (27,40), skewing of macrophage polarization (41), influencing phagocytosis (27,(42)(43)(44), and regulation of both extracellular and intracellular TLR activation (27,40,(45)(46)(47)(48)(49). Due to this plethora of effects, it is perhaps not surprising that the reduced expression or total lack of cathelicidins is correlated with increased risk of infection (50,51) but also has an impact on the development of autoimmune diseases (52)(53)(54)(55).…”

Section: Cathelicidinsmentioning

confidence: 99%

Cathelicidins Modulate TLR-Activation and Inflammation

et al. 2020

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Cathelicidins are short cationic peptides that are part of the innate immune system. At first, these peptides were studied mostly for their direct antimicrobial killing capacity, but nowadays they are more and more appreciated for their immunomodulatory functions. In this review, we will provide a comprehensive overview of the various effects cathelicidins have on the detection of damage-and microbe-associated molecular patterns, with a special focus on their effects on Toll-like receptor (TLR) activation. We review the available literature based on TLR ligand types, which can roughly be divided into lipidic ligands, such as LPS and lipoproteins, and nucleic-acid ligands, such as RNA and DNA. For both ligand types, we describe how direct cathelicidin-ligand interactions influence TLR activation, by for instance altering ligand stability, cellular uptake and receptor interaction. In addition, we will review the more indirect mechanisms by which cathelicidins affect downstream TLR-signaling. To place all this information in a broader context, we discuss how these cathelicidin-mediated effects can have an impact on how the host responds to infectious organisms as well as how these effects play a role in the exacerbation of inflammation in auto-immune diseases. Finally, we discuss how these immunomodulatory activities can be exploited in vaccine development and cancer therapies.

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Identification of human cathelicidin peptide LL-37 as a ligand for macrophage integrin α<sub>M</sub>β<sub>2</sub> (Mac-1, CD11b/CD18) that promotes phagocytosis by opsonizing bacteria

Cited by 28 publications

References 58 publications

The Network of Colonic Host Defense Peptides as an Innate Immune Defense Against Enteropathogenic Bacteria

The Network of Colonic Host Defense Peptides as an Innate Immune Defense Against Enteropathogenic Bacteria

The Role of Macrophages in Staphylococcus aureus Infection

Cathelicidins Modulate TLR-Activation and Inflammation

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