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A more recent version of this article appeared on June 1, 2006

Published online before print April 7, 2006
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© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.0206079


Received for publication February 3, 2006.
Revised March 6, 2006.
Accepted for publication March 12, 2006.


Article

Macrophage nutriprive antimicrobial mechanisms

Rui Appelberg @

Laboratory of Microbiology and Immunology of Infection, IBMC-Institute for Molecular and Cell Biology and ICBAS-Instituto de Ciências Biomédicas de Abel Salazar, University of Porto, Portugal

@ To whom correspondence should be addressed. E-mail: rappelb{at}ibmc.up.pt.


   Abstract

In addition to oxidative and antibiotic mechanisms of antimicrobial activity, macrophages are able to deprive intracellular pathogens of required nutrients. Thus, microbial killing may not rely only in the toxic environment the microbe reaches but also may result from the scarcity of nutrients in the cellular compartment it occupies. Here, we analyze evidence for such nutriprive (from the latin privare, to deprive of nutrients), antimicrobial mechanisms. Although the direct analysis of nutrient availability is most often not feasible, indirect evidence of lack of nutrients in the microbial organelles has been inferred from the study of mutants, the analysis of gene expression, and the consequences of changing the intracellular location of the pathogen. We propose that according to the microbe and its survival strategy, different mechanisms to impede access to nutrients may be constitutively present or may be induced by cytokines and other pathways. Thus, membrane transporters may remove nutrients from vacuolar compartments, and enzymes may degrade some growth factors. A series of diverse compounds may sequester other molecules required for microbial growth, as exemplified by the action of iron chelators. Modulation of vesicular trafficking may prevent the fusion of certain vesicles containing nutrients with those containing the pathogen, counteracting the evasion strategies of the pathogen. The understanding of these mechanisms will certainly help in designing new therapeutic and prophylactic approaches to preventing infectious diseases.

Key Words: nutrient




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