Staphylococcus aureusBiofilms Prevent Macrophage Phagocytosis and Attenuate Inflammation In Vivo

Abstract

Biofilms are complex communities of bacteria encased in a matrix composed primarily of polysaccharides, extracellular DNA, and protein. Staphylococcus aureus (S. aureus) can form biofilm infections, which are often debilitating due to their chronicity and recalcitrance to antibiotic therapy. Currently, the immune mechanisms elicited during biofilm growth and their impact on bacterial clearance remains to be defined. We utilized a mouse model of catheter-associated biofilm infection to assess the functional importance of Toll-like receptors 2 and 9 in the host immune response during biofilm formation, since ligands for both receptors are present within the biofilm. Interestingly, neither receptor impacted bacterial density or inflammatory mediator secretion during biofilm growth in vivo, suggesting that S. aureus biofilms circumvent these traditional bacterial recognition pathways. Several potential mechanisms were identified to account for biofilm evasion of innate immunity, including significant reductions in IL-1β, TNF-α, CXCL2, and CCL2 expression during biofilm infection compared to the wound healing response elicited by sterile catheters, limited macrophage invasion into biofilms in vivo, and a skewing of the immune response away from a microbicidal phenotype as evidenced by decreases in iNOS expression concomitant with robust arginase-1 induction. Co-culture studies of macrophages with S. aureus biofilms in vitro revealed that macrophages successful at biofilm invasion displayed limited phagocytosis and gene expression patterns reminiscent of alternatively activated M2 macrophages. Collectively, these findings demonstrate that S. aureus biofilms are capable of attenuating traditional host proinflammatory responses, which may explain why biofilm infections persist in an immunocompetent host.

Cigarette Smoke Extract–Exposed Methicillin-Resistant Staphylococcus aureus Regulates Leukocyte Function for Pulmonary Persistence

“…In both cell types, CSE-USA300 exhibited significantly improved abilities to evade phagocytic uptake and intracellular killing, as judged by the enumeration of unphagocytosed extracellular CFUs in the cell-free supernatants or gentamicinprotected intracellular CFUs, respectively. Because CSE exposure upregulates staphylococcal biofilm formation, which plays a role in the evasion of phagocytosis and the subsequent bacterial persistence in an immunocompetent host (11,40), we propose that CSE-mediated induction of spa gene expression is yet another mechanism underlying this improved evasion of phagocytosis by CSE-USA300.…”

Accumulation-Associated Protein Enhances Staphylococcus epidermidis Biofilm Formation under Dynamic Conditions and Is Required for Infection in a Rat Catheter Model

“…Although these components have unique structural characteristics, PIA-, Embp-, and Aap-dependent biofilms all are resistant to phagocytosis due to their ability to inhibit NF-B activation and interleukin-1␤ (IL-1␤) production (15,16). Recently, it also was demonstrated that S. aureus biofilms skew the immune response, generating alternatively activated macrophages (17,18) that promote a fibrotic rather than bactericidal response, thereby facilitating bacterial persistence. All of these factors, i.e., ineffectiveness of antimicrobial therapy, alteration of host immune responses, and underlying patient health status, complicate treatment, often leading to chronic infections (19,20).…”

Acinetobacter baumannii biofilm resistance mechanisms and prevention and control of progress

“…The expression of complement transformation, neutrophil respiration and macrophage phagocytosis induced by biofilm significantly decreases. [26] The Acinetobacter baumannii in biofilms can grow under the protection of alginate, and it is not easy to be removed. At the same time, the biofilm bacteria can stimulate the body to produce more antibodies, which makes it easier to form immune complexes with the corresponding soluble antigen to damage the surrounding body tissues, even aggravate the damage.…”