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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 blocking antibodies on Pre-PDT response.Comparison of the area under the RLU curve (AUC) in the Pre-PDT (−1d) + each antibody groups and the Pre-PDT (−1d) group. These values were determined from the time courses shown in Figure S3. n = 5 each. *P<0.05, **P<0.01.
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pone-0039823-g010: Effect of blocking antibodies on Pre-PDT response.Comparison of the area under the RLU curve (AUC) in the Pre-PDT (−1d) + each antibody groups and the Pre-PDT (−1d) group. These values were determined from the time courses shown in Figure S3. n = 5 each. *P<0.05, **P<0.01.

Mentions: The suppressive effect of Pre-PDT for the development of infection was abrogated by the administration of neutralizing antibodies for chemotactic factors that are associated with the neutrophil accumulation into the infectious site, except for an anti-interleukin-6 (IL-6) antibody (Supp. data 3). In the comparison of AUC, anti-macrophage-inflammatory-protein 2 (anti-MIP-2) antibody significantly reduced the Pre-PDT effect (Fig. 10). The other antibodies showed a tendency to reduce the Pre-PDT effect; however, their AUC values were not significantly different from that in the Pre-PDT (−1d) group (Fig. 10). SN50 [38], which is an inhibitor of nuclear factor-kappa B (NF-κB, a transcription factor which is closely related to the initial inflammatory reaction), also showed a tendency to reduce the Pre-PDT effect; however, the AUC value was not significantly different from that in the Pre-PDT (−1d) group (Fig. 10).


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 blocking antibodies on Pre-PDT response.Comparison of the area under the RLU curve (AUC) in the Pre-PDT (−1d) + each antibody groups and the Pre-PDT (−1d) group. These values were determined from the time courses shown in Figure S3. n = 5 each. *P<0.05, **P<0.01.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0039823-g010: Effect of blocking antibodies on Pre-PDT response.Comparison of the area under the RLU curve (AUC) in the Pre-PDT (−1d) + each antibody groups and the Pre-PDT (−1d) group. These values were determined from the time courses shown in Figure S3. n = 5 each. *P<0.05, **P<0.01.
Mentions: The suppressive effect of Pre-PDT for the development of infection was abrogated by the administration of neutralizing antibodies for chemotactic factors that are associated with the neutrophil accumulation into the infectious site, except for an anti-interleukin-6 (IL-6) antibody (Supp. data 3). In the comparison of AUC, anti-macrophage-inflammatory-protein 2 (anti-MIP-2) antibody significantly reduced the Pre-PDT effect (Fig. 10). The other antibodies showed a tendency to reduce the Pre-PDT effect; however, their AUC values were not significantly different from that in the Pre-PDT (−1d) group (Fig. 10). SN50 [38], which is an inhibitor of nuclear factor-kappa B (NF-κB, a transcription factor which is closely related to the initial inflammatory reaction), also showed a tendency to reduce the Pre-PDT effect; however, the AUC value was not significantly different from that in the Pre-PDT (−1d) group (Fig. 10).

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