Nature Medicine | Spoonful of Medicine

Something for the weekend

A couple of days ago I was saying that the problem with blogging (at least for me) is lack of discipline. So I figured that one way to become a bit more disciplined, and hopefully post stuff that people will find of interest, would be to write a brief entry every time I come across a paper that I think is particularly interesting. I’m calling this category of entries “Journal club” for lack of a better name, as I don’t think I want to (nor could) write an extensive critique of the paper in question. Instead, the purpose of doing this is to flag a paper as something that is of interest to an editor of Nature Medicine, and let those of you who work in the relevant field do the detailed evaluation of the contribution.

To get things rolling, here’s three papers:

1) A study by Stephen Hauser and his colleagues in the NEJM reports that rituximab, a drug used for the treatment of non-Hodgkin lymphoma and rheumatoid arthritis, could also be useful to treat multiple sclerosis. Their clinical trial involved 104 people, 69 of whom received two one-gram doses of the drug (which acts by depleting CD20+ B cells). The trial lasted 48 weeks and showed a reduction in the number of inflammatory brain lesions and clinical relapses in the treated patients versus the controls over this time period. Although the trial wasn’t designed to establish long-term safety or efficacy, it is indeed promising for people with MS.

2) In Immunity, Jackson Egen and his colleagues report on their use of high-resolution multiplex static imaging and intravital multiphoton microscopy to give us an unprecedented look at granulomas — masses of inflammatory cells that arise owing to the persistence of an infectious agent in host tissue and that are critical for host protection.

Granulomas, which are often seen in people with tuberculosis, contain different cell types including lymphocytes, macrophages and fibroblasts. In their study, the authors found that, after infection with Mycobacterium bovis, Kupffer cells in the liver capture circulating bacteria and subsequently form the nucleus of a new granuloma by recruiting uninfected liver-resident macrophages and blood-derived monocytes. Within the granuloma, these cells set up an immobile matrix that attracts a dynamic population of T cells in a TNF-alpha-dependent manner. You ought to check out their movies.

3) To continue with the microbiology theme and the topic of the interaction of bacteria with host tissue, Science just published a study on the mechanism whereby tissue abscesses can inhibit bacterial growth. Brian Corbin and his colleagues found that calprotectin — a neutrophil-derived protein — can stall the growth of Staphylococcus aureus inside an abscess. Mechanistically, the effect of calprotectin depended on its ability to chelate Zn2+ and Mn2+, thereby interfering with the transcriptional machinery of the bacterium. In vivo, mice lacking calprotectin had abscesses with higher levels of metals that seemed to favor staphylococcal proliferation. Whether metal chelation can work as a general strategy to inhibit bacterial growth inside an abscess remains to be seen, but the possibility is certainly tantalizing.

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