Intracellular replication of Streptococcus pneumoniae inside splenic macrophages serves as a reservoir for septicaemia.
Ercoli G, Fernandes VE, Chung WY, Wanford JJ, Thomson S, Bayliss CD, Straatman K, Crocker PR, Dennison A, Martinez-Pomares L, Andrew PW, Moxon ER, Oggioni MR
Nat Microbiol. May 2018. doi: 10.1038/s41564-018-0147-1
COMMENT: This is a very interesting study analysing how intracellular Streptococcus pneumoniae dividing inside CD169+ splenic macrophages are the origin of intravenous induced Sepsis in mice:
In experimental pneumococcal murine intravenous infection, an initial reduction of bacteria in the blood is followed hours later by a fatal septicaemia. These events represent a population bottleneck driven by efficient clearance of pneumococci by splenic macrophages and neutrophils, but as we show in this study, accompanied by occasional intracellular replication of bacteria that are taken up by a subset of CD169+ splenic macrophages. In this model, proliferation of these sequestered bacteria provides a reservoir for dissemination of pneumococci into the bloodstream, as demonstrated by its prevention using an anti-CD169 monoclonal antibody treatment.
This fact could have important implications for treatment. The pathogen should be susceptible to the antibiotic but the antibiotic should also be able to enter in the Macrophage in this model:
macrolides, which effectively penetrate macrophages, prevented septicaemia, whereas beta-lactams, with inefficient intracellular penetration, failed to prevent dissemination to the blood.
Our findings define a shift in our understanding of the pneumococcus from an exclusively extracellular pathogen to one with an intracellular phase. These findings open the door to the development of treatments that target this early, previously unrecognized intracellular phase of bacterial sepsis.
In summary, these findings seem to be very relevant because unveil potentially key factors:
- Importance of intracellular status for this pathogen
- Very relevant potential implications for treatment