Clinical Streptococcus pneumoniae isolates induce differing CXCL8 responses from human nasopharyngeal epithelial cells which are reduced by liposomes

Abstract

BackgroundStreptococcus pneumoniae causes several human diseases, including pneumonia and meningitis, in which pathology is associated with an excessive inflammatory response. A major inducer of this response is the cholesterol dependent pneumococcal toxin, pneumolysin. Here, we measured the amount of inflammatory cytokine CXCL8 (interleukin (IL)-8) by ELISA released by human nasopharyngeal epithelial (Detroit 562) cells as inflammatory response to a 24 h exposure to different pneumococcal strains.ResultsWe found pneumolysin to be the major factor influencing the CXCL8 response. Cholesterol and sphingomyelin-containing liposomes designed to sequester pneumolysin were highly effective at reducing CXCL8 levels from epithelial cells exposed to different clinical pneumococcal isolates. These liposomes also reduced CXCL8 response from epithelial cells exposed to pneumolysin knock-out mutants of S. pneumoniae indicating that they also reduce the CXCL8-inducing effect of an unidentified pneumococcal virulence factor, in addition to pneumolysin.ConclusionThe results indicate the potential of liposomes in attenuating excessive inflammation as a future adjunctive treatment of pneumococcal diseases.Electronic supplementary materialThe online version of this article (doi:10.1186/s12866-016-0777-5) contains supplementary material, which is available to authorized users.

Streptococcus pneumoniae burden and nasopharyngeal inflammation during acute otitis media

“…Secretion of inflammatory cytokines, however, can be attributed to any of the cell types present in the NP at the time of sample collection, including epithelial cells and T cells. [34][35][36] However, human neutrophils are known to produce inflammatory cytokines in their own right; in particular, IL-8 and TNF-a. 37,38 We observed that the transcription of IL-8 and TNF-a mRNA in nasal wash pellets (attributable mainly to neutrophils) correlated with the concentrations of these cytokines in the NP.…”

Critical Parameters for the Development of Novel Therapies for Severe and Resistant Infections—A Case Study on CAL02, a Non-Traditional Broad-Spectrum Anti-Virulence Drug

“…In vitro experiments demonstrated the positive impact of CAL02 on cell protection (protection against cell lysis and cell necrosis) and on inflammatory response (e.g., reduction of IL-8 and IL-1beta release), using cell lines as broad as human THP-1 monocytes, human peripheral blood mononuclear cells, bronchial and pharyngeal epithelial cells, HEK 293 epithelial cells, human umbilical vein endothelial cells (HUVEC), and erythrocytes. Cells were exposed to purified bacterial virulence effectors of different classes or to bacterial culture supernatant (i.e., to the secretome, which contains the full range of virulence effectors secreted by the bacterium), or directly exposed to the bacteria [6,9,10,24]. In vivo studies included acute models of infection caused by Gram-positive (S. aureus and S. pneumoniae) and Gram-negative (P. aeruginosa) bacteria, including resistant strains [6,9,10,25,26].…”

Tailored Liposomal Nanotraps for the Treatment of Streptococcal Infections

“…Taking advantage of cholesterol binding, we and others have developed liposomal nanotraps, composed of puri ed lipids, or nanosponges, containing a polymeric core wrapped in a cell-derived lipid bilayer, to neutralize bacterial exotoxins. [15,[19][20][21] Liposomal nanotraps are empty vesicular structures made up of one or more lipid bilayers. They provide an environment, which mimics the in vivo toxin target, in order to divert the toxins from attacking a host cell.…”