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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

Time course of intrarticular leukocytes.Comparison of time courses of intraarticular leukocyte counts in the Pre-PDT (āˆ’1d) group and the PS-IR- group. nā€Š=ā€Š5 each. *P<0.05, **P<0.01.
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pone-0039823-g009: Time course of intrarticular leukocytes.Comparison of time courses of intraarticular leukocyte counts in the Pre-PDT (āˆ’1d) group and the PS-IR- group. nā€Š=ā€Š5 each. *P<0.05, **P<0.01.

Mentions: In the Pre-PDT (āˆ’1d) group, intra-articular leukocyte counts were not increased immediately after Pre-PDT (at āˆ’1d) and 1 day after Pre-PDT (at 0d). However, counts were gradually increased from 2 hours after lux-MRSA inoculation and reached an extremely high level 1 day after the MRSA inoculation, then gradually decreased (Fig. 9), correlating with the results shown in Fig. 8. On the other hand, in the PS-IR- group, although intra-articular leukocytes were not increased 2 hours after MRSA inoculation (at 2h), then gradually increased from 1 day after the inoculation for the whole period of study until the last observation, indicating the protraction of the course of arthritis (Fig. 9).


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)

Time course of intrarticular leukocytes.Comparison of time courses of intraarticular leukocyte counts in the Pre-PDT (āˆ’1d) group and the PS-IR- group. nā€Š=ā€Š5 each. *P<0.05, **P<0.01.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0039823-g009: Time course of intrarticular leukocytes.Comparison of time courses of intraarticular leukocyte counts in the Pre-PDT (āˆ’1d) group and the PS-IR- group. nā€Š=ā€Š5 each. *P<0.05, **P<0.01.
Mentions: In the Pre-PDT (āˆ’1d) group, intra-articular leukocyte counts were not increased immediately after Pre-PDT (at āˆ’1d) and 1 day after Pre-PDT (at 0d). However, counts were gradually increased from 2 hours after lux-MRSA inoculation and reached an extremely high level 1 day after the MRSA inoculation, then gradually decreased (Fig. 9), correlating with the results shown in Fig. 8. On the other hand, in the PS-IR- group, although intra-articular leukocytes were not increased 2 hours after MRSA inoculation (at 2h), then gradually increased from 1 day after the inoculation for the whole period of study until the last observation, indicating the protraction of the course of arthritis (Fig. 9).

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