Table 3.
Summary of molecules and pathways that regulate the inflammatory responses to bacteria in wounds.
| Molecule/Pathway | Wound Model | Bacterial Species | Host Response | Effects on Wound Healing | Reference |
|---|---|---|---|---|---|
| Leukotriene B4 (LTB4)/BLT1 activity | Mouse subcutaneous wound | S. aureus USA300 LAC | Produced by skin macrophages. ↑Neutrophil chemotaxis (CXCL2, CXCL1, CCL8, CCL4, CCL2, and CXCL1) ↑IFN-γ, ↑IL-12p70 ↑NADPH oxidase bactericidal activity ↓Chronic inflammation (RAGE, TIM, CXCL2, IFN-γ, MMP12, and CCL8) |
Organized abscess formation ↑Bacterial clearance |
(147) |
| Diabetic mouse skin wound (undefined) | S. aureus USA300 LAC | ↑LTB4/BLT1 activity ↑Macrophage and neutrophil infiltration ↓Localization to abscess Early infection: ↑ICAM-1, ↑MCP3, ↑IL-33, ↑IL-12p70, ↑IL-1α, ↑RAGE, ↓CXCL1, ↓CXCL2, ↓MIP1β, ↓CCL2, ↓IL-1β, ↓P-selectin Late infection: ↑CXCL1, ↑CCL2, ↑CCL8, ↑MCP3, ↑MIP1β, ↑P-selectin, ↑ICAM-1, ↑IL-1α, ↑IL-33, ↓IL-12p70, ↓RAGE |
↑Abscess size with diffuse immune cell organization ↑Bacterial burden |
(148) | |
| Receptor for Advanced Glycation End Products (RAGE) | Mouse subcutaneous wound | S. aureus SH1000 | ↓MPO, ↓MCP-1, ↓HMGB1, ↓IL-6, and ↓TNF-α in skin prior to infection ↓Blood neutrophil and peritoneal macrophage infiltration |
Severe open skin lesions ↓Abscess formation ↑Bacterial burden |
(149) |
| Myeloid peroxisome proliferation activator receptor γ (PPARγ) | Mouse subcutaneous wound | S. aureus SF8300 | For inflammation➔ resolution phase Formation of a glucose-depleted, hypoxic fibrotic abscess |
↑Bacterial clearance of established infection that failed to clear during the inflammatory phase | (150) |
| miR-142 | Mouse excisional wound | S. aureus NBRC 100910 | ↑miR-142-3p and miR-142-5p expression by infiltrating neutrophils and macrophages ↑Neutrophil recruitment and timely phagocytosis |
Timely resolution of abscess Protection against horizontal transmission of infection |
(151) |
| Myeloid differentiation primary response 88 (MyD88) | Mouse ear pinna intradermal wound | S.aureus Newman | Resident dermal macrophages sense S.aureus via myD88 For early recruitment and regulation of PMNs |
Timely control and clearance of infection | (152) |
| IL-33 | Patients with abscesses due to MRSA. N=3 Mouse intradermal wound |
S. aureus CMCC(B)26003 | ↑IL-33 in human skin samples ↑iNOS in murine skin |
↓Lesion size ↓Bacterial burden |
(153) |
| Neutrophil-derived IL-1β/IL-1R signaling | Mouse intradermal wound | S. aureus SH1000 ALC2906 | Induces expression of genes associated with neutrophil chemotaxis IL-1β is produced by neutrophils. TLR2, NOD2, and FPR1 aid in IL-1β production |
↑Abscess formation | (154) |
| Proline-rich kinase (Pyk2) | Mouse skin abscess. Air-filled pouches in the dermis infected with bacteria |
S. aureus (unknown strain) | ↑PMN activation ↑MPO, ↑MMP9 |
↑Bacterial clearance | (155) |
| iNOS | Mouse full-thickness skin incisional and excisional wound | HK polymicrobial culture of S. aureus, coagulase-negative Staphylococcus, Enterococcal species, P. mirabilis previously isolated from normal mouse skin flora | ↑IFN-γ from lymphocytes ↑iNOS |
NA | (156) |
NA, not applicable; MRSA, methicillin resistant S. aureus; MPO, myeloperoxidase; MCP-1, monocyte chemoattractant protein 1 (MCP-1); HMGB1, high mobility group box protein 1; FPR, formyl peptide receptor; iNOS, inducible nitric oxide synthase; PMN, polymorphonuclear leukocytes; MMP, matrix metalloproteinase; HK, heat-killed.