Although the primary objective of aPDT is the inactivation or elimination of pathogens in infectious settings, its influence on the host immune response is equally significant. In addition to microbial clearance, aPDT may confer secondary benefits such as accelerated wound healing, modulation of inflammation, and broader immunoregulatory effects. The immunomodulatory properties of PDT have been extensively characterized in oncology, with numerous reviews documenting diverse and favorable immune outcomes. Comparable advantages may also be harnessed in the treatment of microbial infections, as demonstrated by the studies summarized in Table 5.
Table 5. Overview of studies assessing the immunomodulatory effects of aPDT.
PS conditions | Targeted microorganism(s) | Observation(s) | Outcome | Reference |
TBO, Diode laser, 630 nm | E. coli and P. aeruginosa | Reduction of LPS-mediated release of proinflammatory cytokines IL-6 and IL-8 from PBMC | + | |
MB, Diode Laser, 670 nm | P. gingivalis | Complete IL-1β and near-complete TNF-α inactivation | + | |
Penothiazine, N.C. | N.C. | Decreased pro-inflammatory cytokines TNF-α and RANKL in patients with chronic periodontitis | + | |
HMME, N.C. | N.A. | Induction of macrophage apoptosis | ± | |
MB, Xenon light source, 660 nm | S. aureus | In vivo neutrophil accumulation and infiltration at the infection site in mice | − | |
Pl-cp6, Diode laser, 660 nm | P. aeruginosa | In vivo reduced inflammatory cell infiltration, downregulation of pro-inflammatory cytokines TNF-α and IL-6 in mice | + | |
Ce6, N.C., 670 nm | ???? | Unchanged IL-1β production, decreased IL-6, and IL-8 production by human keratocytes | + | |
ICG, Diode laser, 805 nm | N.A. | Decreased IL-6 and IL-8 expression in oral epithelial cell lines in the presence of Escherichia coli-derived LPS after the application of light | + | |
Photofrin®, MB, N.C. | S. aureus | In vitro reduced neutrophil viability with Photofrin®, low toxicity with MB. In vivo decreased neutrophil count with systemic and local administration of Photofrin®, and neutrophil accumulation with MB in mice | ± | |
N.C., Diode Laser, 670 nm, 3 applications | Tannerella forsythia, P. gingivalis | Decreased IL-1β levels, unchanged IL-10, and TNF-α levels in gingival crevicular fluid samples in patients with aggressive periodontitis | + | |
Pl-cp6, Cold laser, 660 nm | P. aeruginosa | In vivo reduction of expression of pro-inflammatory cytokines (TLR-4, NF-kB, IL-1α, IL-1ß, and IL-2) and increased expression of cell proliferation markers (FGF-2 and ALP) in mice | + | |
MB, Diode laser, 655 nm | S. aureus | No effect on the release of pro-inflammatory cytokines IL-6, IL-1β, and TNF-α by TLRs. Increased release of IL-1β by TLR, and Hspa1b gene up-regulation in fibroblasts. In vivo indirect induction of neutrophil migration via stimulation of fibroblast-macrophage interaction in a murine model | + | |
Cur, LED, 480 nm | N. A. | No in vivo change in IL-1β and IL-6 cytokine production by fibroblasts in mice | 0 | |
MB, Diode laser, 660 nm | P. gingivalis | In vivo increased hemocyte density in Galleria mellonella larvae | + | |
MB, laser, 670 nm | P. gingivalis & Tannerella forsythia | No in vivo change in crevicular cytokine levels (IL-1β, IL-2, IL-4, IL-5, IL-6, IL-12p70, IL-13, IFN-γ, TNF-α, and GM-CSF) in periodontal pockets in patients with chronic periodontitis | 0 | |
MB, Diode laser, 660 nm | P. gingivalis, Fusobacterium nucleatum | In vitro and in vivo induction of apoptosis of over-infiltrated macrophages in rats with periodontitis | + | |
MB, Low-level laser, 660 nm, 4 applications | Aggregatibacter actinomycetemcomitans, P. gingivalis, Prevotella nigrescens, and Fusobacterium nucleatum | In vivo reduction of TNF-α and IL-6 in rats with periodontitis. No significant effect on RANKL or on the decrease in TRAP-positive osteoclasts. | + | |
MB, LED, 660 nm | C. albicans | Increased neutrophil adhesion and impaired phagocytic activity | − | |
Chlorophyll derivatives, Xenon light, 185-2000 nm | E. coli & S. aureus | Decreased pro-inflammatory TNF-α and IL-6 cytokine levels upon photo-activation | + | |
MB, Diode laser, 670 nm | P. gingivalis & T. forsythia | In vivo reduction of pro-inflammatory TNF-α and IL-6 cytokines in patients with generalized gingivitis | + | |
5-ALA, Laser light, N.C. | Fonsecaea monophora, S. aureus, & C. albicans | In vivo enhanced immune response and increased hemocyte counts in infected Galleria mellonella larvae. No effect on hemocyte activity in vitro against S. aureus and C. albicans. No inhibitory effect against Fonsecaea monophora in vitro of hemolymphs from PDT-treated larvae | ± | |
PpIX, LED, 410-490 nm | N.A. | In vivo increased pro-inflammatory TNF-α and anti-inflammatory IL-10 cytokine, and decreased IL-6 cytokine production by macrophages in mice in the presence of E. coli-derived LPS. No macrophage lipid peroxidation. Induction of DNA damage in macrophages. | ± | |
5-ALA, LED, 630 nm | P. aeruginosa | In vivo macrophage activation and promotion of wound healing in infected mice | + | |
ICG, Diode laser, 970 nm | N.A. | Unchanged mRNA levels of IL-6 (pro-inflammatory cytokines), VEGF (blood vessel), RunX2 (bone formation), and Nell-1 (bone regeneration) in aPDT-treated or untreated patients with periodontitis | 0 | |
HY, Incoherent light source, 450-720 nm | N.A. | Decreased release of cytokines IL-8, IL-11, IL-19, IL-22, and MMP-1 by primary epidermal keratinocytes and primary dermal fibroblasts. Unchanged release for IL-2 and IL-10 cytokines | ± | |
Brazilian green propolis, N.C. | S. aureus | In vivo increased recruitment of polymorphonuclear cells/neutrophils to the infected tissue, and increased count of cytokines in the draining retromaxillary lymph node in mice | ± | |
MB, MBSD, N.A., 633 nm, 4 cycles | SARS-CoV-2 B.1 and B.1.617.2, ZIKV, VACV, AaPV, and GAKV | In vivo decreased peribronchial inflammation, improved histological scores in mice | + | |
PDZ, LED, N.C., 5 cycles | C. albicans | In vivo increased production of IL-6, TNF-α cytokines and MCP-1 chemokines in mice | ± | |
Abbreviations: AaPV: Apodemus agrarius Paramyxovirus; Cur: curcumin GAKV: Henipa-like Gamak virus; GM-CSF: Granulocyte-macrophage colony-stimulating factor; HMME: hematoporphyrin monomethyl ether; HY: hypericin, 4,5,7,4′,5′,7′-hexahydroxy-2,2′-dimethylnaphthodianthrone; ICG: indocyanine green, Periogreen®; IFN-γ: Interferon gamma; IL: interleukin; LED: light-emitting diode; LPS: lipopolysaccharide; MB: methylene blue; MBSD: Methylene blue-based nanocomplex; MMP: matrix metalloproteinases; N.A.: not applicable; N.C.: not communicated; PBMC: Peripheral blood mononuclear cell; PDZ: Photodithazine®; Pl–cp6: poly-L-lysine-conjugated chlorin p6; PpIX: protoporphyrin IX; RANKL: receptor activator of nuclear factor- κB ligand; RunX2: runt-related transcription factor 2; TNF-α: tumor necrosis factor; VACV: Vaccinia virus; VEGF: vascular endothelial growth factor; ZIKV: Zika virus; 5-ALA: 5-aminolevulinic acid; +: pro-immunomodulatory; −: immune-dysregulatory; ±: dual/ context-dependent; 0: neutral. | ||||