Extracellular DNA: a major proinflammatory component of Pseudomonas aeruginosa biofilms.
We previously demonstrated that extracellular bacterial DNA activates neutrophils through a CpG- and TLR9-independent mechanism. Biofilms are microbial communities enclosed in a polymeric matrix that play a critical role in the pathogenesis of many infectious diseases. Because extracellular DNA is a key component of biofilms of different bacterial species, the aim of this study was to determine whether it plays a role in the ability of biofilms to induce human neutrophil activation. We found that degradation of matrix extracellular DNA with DNase I markedly reduced the capacity of Pseudomonas aeruginosa biofilms to induce the release of the neutrophil proinflammatory cytokines IL-8 and IL-1beta (>75%); reduced the upregulation of neutrophil activation markers CD18, CD11b, and CD66b (p < 0.001); reduced the number of bacteria phagocytosed per neutrophil contacting the biofilm; and reduced the production of neutrophil extracellular traps. Consistent with these findings, we found that biofilms formed by the lasI rhlI P. aeruginosa mutant strain, exhibiting a very low content of matrix extracellular DNA, displayed a lower capacity to stimulate the release of proinflammatory cytokines by neutrophils, which was not decreased further by DNase I treatment. Together, our findings support that matrix extracellular DNA is a major proinflammatory component of P. aeruginosa biofilms.
Fuxman Bass
Juan I
JI
Departamento de Inmunología, Instituto de Investigaciones Hematológicas and Instituto de Estudios Oncológicos Fundación Maissa, Academia Nacional de Medicina, Buenos Aires, Argentina.
Russo
Daniela M
DM
Gabelloni
Maria L
ML
Geffner
Jorge R
JR
Giordano
Mirta
M
Catalano
Mariana
M
Zorreguieta
Angeles
A
Trevani
Analía S
AS
D018441:Biofilms / Q000254:growth & development*; D016207:Cytokines / Q000096:biosynthesis; D004269:DNA, Bacterial / Q000276:immunology*; D045604:Extracellular Fluid / Q000737:chemistry / Q000382:microbiology; D006801:Humans; D018613:Microscopy, Confocal; D018375:Neutrophil Activation / Q000276:immunology*; D009504:Neutrophils / Q000276:immunology* / Q000378:metabolism; D011550:Pseudomonas aeruginosa / Q000502:physiology*
D016207:Cytokines; D004269:DNA, Bacterial