Biofilm-Leukocyte Cross-Talk: Impact on Immune Polarization and Immunometabolism

Abstract

Biofilms are bacterial communities contained within an extracellular matrix, which can colonize both native tissues and artificial surfaces. In particular, indwelling medical devices and prosthetic implants are targets for biofilm formation because they facilitate bacterial attachment via host proteins that coat the foreign body. Biofilm infections are particularly challenging to treat, since they are not readily cleared by antibiotics, require invasive procedures to eradicate, and are prone to recurrence. It has been demonstrated that biofilm-derived products can actively suppress proinflammatory immune responses, as evident by the recruitment of myeloid-derived suppressor cells and macrophage (MФ) polarization towards an anti-inflammatory state. Recent studies have shown that alterations in leukocyte metabolism shape their inflammatory phenotype and function. For example, anti-inflammatory MФs are biased towards oxidative phosphorylation whereas proinflammatory MФs favor aerobic glycolysis. This review will compare the immune responses elicited by planktonic and biofilm bacterial infections, with a discussion on the metabolic properties of MФs and neutrophils in response to both bacterial growth conditions.

A mouse ear skin model to study the dynamics of innate immune responses against Staphylococcus aureus biofilms

“…We quantified this response for the first time and showed that it is significantly increased with the planktonic form after 4 h, compared to that in control mice. The absence of significant differences between the control and biofilm conditions could have been due to early phagocyte killing, as previously reported [4,5,17]. After 24 h, the inflammatory response was considerable and comparable for the two bacterial forms.…”

“…The immune responses elicited by biofilms have been described as specific and ineffective thus promoting bacterial persistence and the establishment of chronic infections [4]. Different immune evasion mechanisms have been proposed to be involved, including phagocyte direct killing (macrophages, neutrophils), specific recruitment of myeloid-derived suppressor cells (MDSCs) and macrophage polarization towards an anti-inflammatory phenotype [4,5]. These results were mostly obtained during experiments performed in vitro in which biofilms were exposed to monocytes or neutrophils, or both [6].…”

TLR2 and caspase-1 signaling are critical for bacterial containment but not clearance during craniotomy-associated biofilm infection

“…TLR2, but not TLR9, is critical for bacterial containment during S. aureus craniotomy infection Infectious complications after craniotomy are typically not able to be resolved without performing surgery to debride the infected bone flap and surrounding purulent material [28]. This is because bacteria adherent to the bone flap have formed a biofilm, which is recalcitrant to antibiotics and immune-mediated clearance [4,29]. Once the biofilm has been disrupted, by aggressive disinfection of the bone flap intra-operatively or removal if the bone flap cannot be salvaged, the remaining bacteria are antibiotic susceptible, since they become metabolically active.…”

Pseudomonas aeruginosabiofilms display carbohydrate ligands for CD206 and CD209 that interfere with their receptor function

“…Biofilms are major drivers of bacterial pathogenesis in the context of chronic infections. Historically, protection against immune attack alongside antibiotic tolerance, were postulated as the key advantages conferred by these biofilms during infection but research into their role in modulating immunity is gathering momentum (5, 25). In the context of infection, MR and DC-SIGN are considered promoters of regulatory immune mechanisms designed to curtail damaging inflammatory processes and MR and/or DC-SIGN binding are viewed as immune evasion mechanism(s) (11, 12, 26, 27).…”