Saturday, January 17, 2015

Skin fat cell differentiation program has an immunologically-active phase

Staphylococcus aureus (S. aureus) infection represents a major medical issue. Unlike viral or intra-cellular microbial infections, we still do not know much about how immune system defends against extra-cellular microbes.

The research group, led by Richard Gallo at UC San Diego School of Medicine, observed that skin infection with S. aureus induced local adipocyte expansion. 

Analysis of mice deficient in fat cell development (Zfp423nur12 mouse) showed that these mice contained  more S. aureus locally in skin wound as well as systematically, in the spleen.

In vitro analysis of adipocyte differentiation revealed that maturation of pre-adipocytes to adipocytes led to selective expression of anti-microbial peptide, cathelicidin (Camp). Camp expression peaked at days 2-4 in adipocyte differentiation program. 

As a result, adipocyte condition medium could inhibit S. aureus growth in vitro.

In addition, up-regulation of Camp in maturing adipocytes was in response to S. aureus infectionAs expected, a medium supplemented with adipocyte tissue extract from Camp-KO could not inhibit S. aureus growth.

Finally, adipogenesis deficient Zfp423nur12 mouse did not up-regulate Camp in response to S. aureus.

In summary, these results indicate that S. aureus skin infection activates pre-adipocyte to adipocyte differentiation program and induces Camp, Cathelicidin, anti-microbial peptide expression that inhibits S. aureus growth and prevents it's systemic spread.

The authors suggest that at this early stage of S. aureus skin infection (day 2-7) adipocyte-derived Camp expression dominates the host defense. 

However, in my opinion, to clearly rule out the role of innate immune system (neutrophils, macrophages) it would necessary to repeat these experiments with anti-Gr-1 antibody (neutrophil depletion) or macrophage-deficient mouse models or immune system-specific Camp deficiency (BM chimera).   

David Usharauli

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