Photodynamic Therapy Can Induce a Protective Innate Immune Response against Murine Bacterial Arthritis via Neutrophil Accumulation

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.

Porphyrin-based cationic amphiphilic photosensitisers as potential anticancer, antimicrobial and immunosuppressive agents

“…In theory, the same vaccination effect described for anticancer PDT should facilitate adaptive immune responses to microbes, but, to the best of our knowledge, this has not yet been experimentally addressed. Nevertheless, in a murine MRSA-mediated arthritis model, Photofrin-mediated PDT stimulated strong neutrophil infiltration, which positively correlated with bacterial killing (Tanaka et al 2012). Neutrophil infiltration could also be triggered by pretreatment, suggesting that the proinflammatory effect of PDT can be separated from its direct effect on microbial killing.…”

“…Like cancer cells, pathogens can be eliminated by the direct killing via oxidative stress and there is some evidence that this also enhances the PDT-mediated immune response to certain bacteria (Tanaka et al 2012). The development of drug resistance is a common problem in many antiviral treatments and chemotheraphies, and antibiotic resistance is an imminent global threat to public health (WHO 2016;Housman et al 2014), so new treatment modalities for these diseases are widely sought after.…”

Biotecnologia Aplicada à Agro&Indústria - Vol. 4

“…Tanaka et al 171 avaliaram os efeitos citotóxicos da TFD sobre os neutró-filos do sangue periférico de murinos utilizando diferentes fotossensibilizadores. Cada fotossensibilizador foi testado em uma concentração que exerceu um efeito máximo bactericida sobre Staphylococcus aureus resistente à meticilina (MRSA).…”

“…Os biossensores mais utilizados para a detecção de micotoxinas são baseados em imunoensaio competitivo ou não competitivo acoplados a diferentes tipos de detectores. Imunossensores acoplados a detectores eletroquímicos 170 , ópticos 171,172 e quimioluminescentes 34 têm sido desenvolvidos para a detecção de fumonisinas. Um biossensor, integrando um imunoensaio de fluxo lateral acoplado a um detector de quimioluminescência enzimática e a um dispositivo de carga-acoplada (DCA) de alta sensibilidade, foi desenvolvido para a detecção de fumonisinas (FB 1 e FB 2 ) em milho.…”

“…O controle da qualidade de grãos, alimentos e rações depende da disponibilidade de métodos rápidos, sensíveis, confiáveis e de baixo custo. 171 A presença do DENV pode ser detectada para fins clínicos e de pesquisa por técnicas sorológicas e moleculares de isolamento viral. Os métodos sorológicos detectam anticorpos contra o DENV e podem ser realizados somente após a fase aguda da doença (após o sexto dia de sintomas aproximadamente).…”