Comparison of the immune response during acute and chronic Staphylococcus aureus infection

Abstract

Staphylococcus aureus bacteria are able to grow in a planktonic state that is associated with acute infections and in biofilms that are associated with chronic infections. Acute infections, such as skin infections, are often self-limiting. However, chronic infections, such as implant infections, can be difficult to clear and may require surgical intervention. The host immune response may contribute to the different outcomes often associated with these two disease types. We used proteomic arrays and two murine models for an initial, descriptive characterization of the contribution of the host immune response to outcomes of acute versus chronic S. aureus disease. We compared the immune responses between a model of self-limiting skin and soft tissue infection caused by the planktonic form of S. aureus versus a model of surgical mesh implant infection, which we show to be caused by a bacterial biofilm. The significantly altered host cytokines and chemokines were largely different in the two models, with responses diminished by 21 days post-implantation in surgical mesh infection. Because bacterial levels remained constant during the 21 days that the surgical mesh infection was followed, those cytokines that are significantly increased during chronic infection are not likely effective in eradicating biofilm. Comparison of the levels of cytokines and chemokines in acute versus chronic S. aureus infection can provide a starting point for evaluation of the role of specific immune factors that are present in one disease manifestation but not the other.

Fig 1. Characterization of S. aureus surgical mesh model of biofilm infection.

(A) Surgical mesh sections were incubated for 24 hours in S. aureus liquid culture before implantation. Shown are mesh implants removed 21 days after implantation compared to CFU levels obtained immediately before implantation (inoculum). Individual implants with mean +/- SD are shown. (B) 1 x 1 cm segments of sterile surgical mesh were incubated in TSB containing RFP-expressing S. aureus for 7 days. A 3D reconstructed confocal microscopy image from 28 optical sections overlaid with differential interference contrast (DIC) image is shown. RFP-expressing S. aureus are red and extracellular DNA is blue (Hoescht 33258). The mesh interface is indicated with the arrow. Scale bar indicates 10 μm. (C) Inoculated or sterile mesh were implanted, and 21 days after implantation, animals were either treated with vancomycin (infected + vancomycin) or left untreated (infected–vancomycin). CFU levels for individual implants +/- SD are shown.

Fig 2. Protein production levels in acute and chronic S. aureus infection.

Data from three independent arrays, each run with pools of three animals, were analyzed. Only proteins that met significance criteria (Log2 fold change (LFC, infected:control) ≤ -1 or ≥ 1, and p ≤ 0.05, one sample t test) in at least one infection type are shown. LFC is represented by the range indicated on the right, with proteins with increased production indicated with green and proteins with decreased production indicated with red. No change relative to control (uninfected) samples is indicated in white.