Abstract
Despite the considerable progress made in recent years, our understanding of the human immune response to microbial biofilms is still poor. The aim of the present study was to compare the in vitro response of human peripheral blood mononuclear cells (PBMC) to biofilms and planktonic cells of Pseudomonas aeruginosa and Staphylococcus epidermidis, two bacterial species particularly relevant in patients with cystic fibrosis or undergoing endovascular catheterization, respectively. PBMC isolated from healthy donors were co-cultured with 24 h-old biofilms or with exponentially growing cells of both species. Following 24 h of co-culture, the expression of early activation markers and the levels of cytokines in the culture supernatants were assessed by flow cytometry, while biofilm biomass and architecture were evaluated by crystal violet staining, CFU count, and confocal microscopy. Around 20% of PBMC was activated in response to both biofilms and planktonic cells of P. aeruginosa. In contrast, planktonic cells of S. epidermidis induced a statistically higher degree of activation than their biofilm counterpart (25% versus 15%; p < 0.01). P. aeruginosa biofilms stimulated pro-inflammatory (TNF-α, IL-1β, IFN-γ, and IL-6) and anti-inflammatory (IL-10) cytokine production at statistically significant levels higher than its planktonic counterpart, while an opposite trend was observed with S. epidermidis. Differences in the architecture of the biofilms and in the number of PBMC infiltrating the biofilms between the two bacterial species may at least partially explain these findings. Collectively, the results obtained highlighted marked differences in the host–cell response depending on the species and the mode of growth (biofilms versus planktonic cultures), allowing speculations on the different strategies adopted by P. aeruginosa and S. epidermidis to persist in the host during the course of chronic infections.
Highlights
It is widely recognized that the host immune response is only partially helpful in clearing biofilm-associated bacteria [14], but a detailed knowledge of the mechanisms involved and of the biofilm-specific properties, eliciting an inefficient immune response as compared to the planktonic life-style is only beginning to be understood
P. aeruginosa and S. epidermidis, two clinically relevant bacterial species whose pathogenicity greatly relies on biofilm formation
P. aeruginosa’s ability to establish many chronic human infections such as chronic lung or wound infections is strictly dependent on biofilm formation that allows the bacterium to adapt to the host, retrieve nutrients and persist for decades in the tissues [20]
Summary
Biofilms are complex bacterial communities encased within an extracellular polymeric substance (EPS) [1]. They have the ability to develop on both host native tissues and artificial surfaces [1]. These latter include a wide variety of implanted medical devices (e.g., indwelling catheters, artificial heart valves, orthopedic prostheses, and dental implants), which are essential tools in modern clinical practice [2]. Due to an intrinsic tolerance of biofilm-embedded bacteria to antimicrobial treatment and clearance by the host immune system, the management of biofilm-associated infections is challenging [3,4]
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