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Photodynamic therapy can induce a protective innate immune response against murine bacterial arthritis via neutrophil accumulation.

Tanaka M, Mroz P, Dai T, Huang L, Morimoto Y, Kinoshita M, Yoshihara Y, Nemoto K, Shinomiya N, Seki S, Hamblin MR - PLoS ONE (2012)

Bottom Line: In the present study, a murine methicillin-resistant Staphylococcus aureus (MRSA) arthritis model using bioluminescent MRSA and polystyrene microparticles was established, and both the therapeutic (Th-PDT) and preventive (Pre-PDT) effects of PDT using methylene blue as photosensitizer were examined.Although Th-PDT could not demonstrate direct bacterial killing, neutrophils were accumulated into the infectious joint space after PDT and MRSA arthritis was reduced.This is the first demonstration of a protective innate immune response against a bacterial pathogen produced by PDT.

View Article: PubMed Central - PubMed

Affiliation: Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, Massachusetts, United States of America.

ABSTRACT

Background: Local microbial infections induced by multiple-drug-resistant bacteria in the orthopedic field can be intractable, therefore development of new therapeutic modalities is needed. Photodynamic therapy (PDT) is a promising alternative modality to antibiotics for intractable microbial infections, and we recently reported that PDT has the potential to accumulate neutrophils into the infected site which leads to resolution of the infection. PDT for cancer has long been known to be able to stimulate the innate and adaptive arms of the immune system.

Methodology/principal findings: In the present study, a murine methicillin-resistant Staphylococcus aureus (MRSA) arthritis model using bioluminescent MRSA and polystyrene microparticles was established, and both the therapeutic (Th-PDT) and preventive (Pre-PDT) effects of PDT using methylene blue as photosensitizer were examined. Although Th-PDT could not demonstrate direct bacterial killing, neutrophils were accumulated into the infectious joint space after PDT and MRSA arthritis was reduced. With the preconditioning Pre-PDT regimen, neutrophils were quickly accumulated into the joint immediately after bacterial inoculation and bacterial growth was suppressed and the establishment of infection was inhibited.

Conclusions/significance: This is the first demonstration of a protective innate immune response against a bacterial pathogen produced by PDT.

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Related in: MedlinePlus

Effect of anti-GR-1 antibody.Comparison of time courses of the bioluminescent intensity in the PS-IR- group, the anti-GR-1 antibody + Th-PDT (50 J/cm2) group and the Th-PDT (50 J/cm2) group. n = 5 each. **P<0.01.
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pone-0039823-g005: Effect of anti-GR-1 antibody.Comparison of time courses of the bioluminescent intensity in the PS-IR- group, the anti-GR-1 antibody + Th-PDT (50 J/cm2) group and the Th-PDT (50 J/cm2) group. n = 5 each. **P<0.01.

Mentions: In the 50 J/cm2 group with neutrophil-depletion using intravenous anti-GR-1 antibody, the consequent bioluminescent intensity was maintained at high levels until 7d, which was similar to that in the PS-IR- group (Fig. 5), indicating that therapeutic effect of PDT was lost when neutrophils were depleted using intravenous anti-GR-1 antibody.


Photodynamic therapy can induce a protective innate immune response against murine bacterial arthritis via neutrophil accumulation.

Tanaka M, Mroz P, Dai T, Huang L, Morimoto Y, Kinoshita M, Yoshihara Y, Nemoto K, Shinomiya N, Seki S, Hamblin MR - PLoS ONE (2012)

Effect of anti-GR-1 antibody.Comparison of time courses of the bioluminescent intensity in the PS-IR- group, the anti-GR-1 antibody + Th-PDT (50 J/cm2) group and the Th-PDT (50 J/cm2) group. n = 5 each. **P<0.01.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3383702&req=5

pone-0039823-g005: Effect of anti-GR-1 antibody.Comparison of time courses of the bioluminescent intensity in the PS-IR- group, the anti-GR-1 antibody + Th-PDT (50 J/cm2) group and the Th-PDT (50 J/cm2) group. n = 5 each. **P<0.01.
Mentions: In the 50 J/cm2 group with neutrophil-depletion using intravenous anti-GR-1 antibody, the consequent bioluminescent intensity was maintained at high levels until 7d, which was similar to that in the PS-IR- group (Fig. 5), indicating that therapeutic effect of PDT was lost when neutrophils were depleted using intravenous anti-GR-1 antibody.

Bottom Line: In the present study, a murine methicillin-resistant Staphylococcus aureus (MRSA) arthritis model using bioluminescent MRSA and polystyrene microparticles was established, and both the therapeutic (Th-PDT) and preventive (Pre-PDT) effects of PDT using methylene blue as photosensitizer were examined.Although Th-PDT could not demonstrate direct bacterial killing, neutrophils were accumulated into the infectious joint space after PDT and MRSA arthritis was reduced.This is the first demonstration of a protective innate immune response against a bacterial pathogen produced by PDT.

View Article: PubMed Central - PubMed

Affiliation: Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, Massachusetts, United States of America.

ABSTRACT

Background: Local microbial infections induced by multiple-drug-resistant bacteria in the orthopedic field can be intractable, therefore development of new therapeutic modalities is needed. Photodynamic therapy (PDT) is a promising alternative modality to antibiotics for intractable microbial infections, and we recently reported that PDT has the potential to accumulate neutrophils into the infected site which leads to resolution of the infection. PDT for cancer has long been known to be able to stimulate the innate and adaptive arms of the immune system.

Methodology/principal findings: In the present study, a murine methicillin-resistant Staphylococcus aureus (MRSA) arthritis model using bioluminescent MRSA and polystyrene microparticles was established, and both the therapeutic (Th-PDT) and preventive (Pre-PDT) effects of PDT using methylene blue as photosensitizer were examined. Although Th-PDT could not demonstrate direct bacterial killing, neutrophils were accumulated into the infectious joint space after PDT and MRSA arthritis was reduced. With the preconditioning Pre-PDT regimen, neutrophils were quickly accumulated into the joint immediately after bacterial inoculation and bacterial growth was suppressed and the establishment of infection was inhibited.

Conclusions/significance: This is the first demonstration of a protective innate immune response against a bacterial pathogen produced by PDT.

Show MeSH
Related in: MedlinePlus