Ação da vitamina D sobre mecanismos bactericidas de neutrófilos humanos desafiados com diferentes cepas de Staphylococcus aureus
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Data
2019-02-28
Autores
Della Coletta, Amanda Manoel [UNESP]
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Editor
Universidade Estadual Paulista (Unesp)
Resumo
Recentemente, a deficiência de vitamina D vem se tornando um problema de abrangência mundial em virtude de hábitos rotineiros da população, como o trabalho por períodos prolongados em ambientes fechados e diminuição da exposição solar. Trabalhos recentes demonstram que a vitamina D age não somente na homeostase do cálcio, mas também na regulação do sistema imune. Diante da multiplicidade de funções dessa vitamina, sua deficiência tem sido associada ao risco de desenvolvimento de uma série de doenças, entre elas doenças infecciosas como as causadas por S. aureus. As infecções por essa bactéria têm trazido expressiva preocupação para a população humana em decorrência do aumento da prevalência de cepas resistentes aos fármacos antibacterianos, dificultando, dessa maneira, o tratamento e contribuindo para a busca de métodos alternativos para combater esse tipo de infecção. Além disso, o S. aureus conta com um potente arsenal de fatores de virulência que contribuem para a evasão da resposta imune do hospedeiro. Nesse contexto, torna-se importante avaliar se a vitamina D pode modular os efeitos bactericidas de neutrófilos humanos através de mecanismos intra e extracelulares, favorecendo, portanto, o combate a infecções, especialmente aquelas causadas por microrganismos resistentes aos principais tratamentos. Dessa maneira, nós demonstramos que neutrófilos tratados com vitamina D e desafiados com duas cepas de S. aureus tiveram um aumento nas taxas de fagocitose e atividade bactericida dependentes da cepa estudada, contribuindo para as propriedades antimicrobianas dos neutrófilos. Além disso, identificamos que indivíduos com níveis séricos de vitamina D deficientes/insuficientes estavam correlacionados com menor liberação de NETs e taxa de fagocitose; enquanto indivíduos com níveis séricos de vitamina D suficientes foram correlacionados com maior liberação de NETs, taxa de fagocitose intermediária e atividade bactericida. Portanto, a vitamina D pode modular a resposta imune inata contra S. aureus principalmente por aumento de taxas fagocíticas e atividade bactericida.
In the last years, vitamin D deficiency has become a worldwide problem due to routine population habits, such as prolonged work indoors and increased use of sunscreen/decreased sun exposure in attempt to avoid high rates of skin cancer. Recent studies demonstrated that vitamin D acts not only on calcium homeostasis, but also on the regulation and function of the immune system. Facing the countless functions of vitamin D, its deficiency has been associated with the risk of development of many diseases, including infectious diseases such as those caused by S. aureus. Infections caused by these bacteria have brought significant concern to the human population due to the increased prevalence of strains resistant to antibiotics, thus making it difficult to treat and contributing to the search for alternative methods to combat this type of infection. In addition, S. aureus have a variety of virulence factors, which confer the ability to evade host immune responses. In this context, it is important to evaluate whether vitamin D can modulate the bactericidal effects of human neutrophils through intra- and extracellular mechanisms, such as phagocytosis, bacterial killing and release of Neutrophil Extracellular Traps (NETs), thus contributing to the response against infections, especially those caused by microorganisms resistant to the main treatments. Thus, we demonstrated that neutrophils treated with Vitamin D and challenged with two strains of S. aureus had an increase in phagocytic rates and bactericidal activity in a dependence of the strain, contributing to neutrophil antimicrobial properties. Besides, we identified that individuals with deficient/insufficient vitamin D serum levels were correlated with lower NETs release and phagocytosis rate; while individuals with sufficient vitamin D serum levels were correlated with higher NETs release, intermediate phagocytosis rate and bactericidal activity. Then, Vitamin D could modulate the innate immune response against S. aureus mainly by phagocytic rates and bactericidal activity. Further studies are needed to better understand the complex capacity of Vitamin D on modulation of the innate immune response.
In the last years, vitamin D deficiency has become a worldwide problem due to routine population habits, such as prolonged work indoors and increased use of sunscreen/decreased sun exposure in attempt to avoid high rates of skin cancer. Recent studies demonstrated that vitamin D acts not only on calcium homeostasis, but also on the regulation and function of the immune system. Facing the countless functions of vitamin D, its deficiency has been associated with the risk of development of many diseases, including infectious diseases such as those caused by S. aureus. Infections caused by these bacteria have brought significant concern to the human population due to the increased prevalence of strains resistant to antibiotics, thus making it difficult to treat and contributing to the search for alternative methods to combat this type of infection. In addition, S. aureus have a variety of virulence factors, which confer the ability to evade host immune responses. In this context, it is important to evaluate whether vitamin D can modulate the bactericidal effects of human neutrophils through intra- and extracellular mechanisms, such as phagocytosis, bacterial killing and release of Neutrophil Extracellular Traps (NETs), thus contributing to the response against infections, especially those caused by microorganisms resistant to the main treatments. Thus, we demonstrated that neutrophils treated with Vitamin D and challenged with two strains of S. aureus had an increase in phagocytic rates and bactericidal activity in a dependence of the strain, contributing to neutrophil antimicrobial properties. Besides, we identified that individuals with deficient/insufficient vitamin D serum levels were correlated with lower NETs release and phagocytosis rate; while individuals with sufficient vitamin D serum levels were correlated with higher NETs release, intermediate phagocytosis rate and bactericidal activity. Then, Vitamin D could modulate the innate immune response against S. aureus mainly by phagocytic rates and bactericidal activity. Further studies are needed to better understand the complex capacity of Vitamin D on modulation of the innate immune response.
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Palavras-chave
Atividade Bactericida, Fagocitose, Redes Extracelulares de Neutrófilos (NETs), Vitamina D, Staphylococcus aureus, Bactericidal Activity, Phagocytosis, Neutrophil Extracellular Traps (NETs), Vitamin D