Phenotypic diversity and emerging new tools to study macrophage activation in bacterial infectious diseases.

Macrophage polarization is a concept that has been useful to describe the different features of macrophage activation related to specific functions. Macrophage polarization is responsible for a dichotomic approach (killing vs. repair) of the host response to bacteria; M1-type conditions are protective, whereas M2-type conditions are associated with bacterial persistence. The use of the polarization concept to classify the features of macrophage activation in infected patients using transcriptional and/or molecular data and to provide biomarkers for diagnosis and prognosis has most often been unsuccessful. The confrontation of polarization with different clinical situations in which monocytes/macrophages encounter bacteria obliged us to reappraise this concept. With the exception of M2-type infectious diseases, such as leprosy and Whipple's disease, most acute (sepsis) or chronic (Q fever, tuberculosis) infectious diseases do not exhibit polarized monocytes/macrophages. This is also the case for commensals that shape the immune response and for probiotics that alter the immune response independent of macrophage polarization. We propose that the type of myeloid cells (monocytes vs. macrophages) and the kinetics of the immune response (early vs. late responses) are critical variables for understanding macrophage activation in human infectious diseases. Explorating the role of these new markers will provide important tools to better understand complex macrophage physiology.

Macrophage polarization and bacterial infections.

PURPOSE OF REVIEW: Macrophages are the first line of defense against pathogens, and the mode of their activation will determine the success or failure of the host response to pathogen aggression. Based on limited numbers of markers, activated macrophages can be classified as classically activated (M1) macrophages that support microbicidal activity or alternatively activated (M2) macrophages that are not competent to eliminate pathogens. The development of high-throughput gene expression methods affords a reappraisal of the concept of macrophage activation in human infectious diseases. RECENT FINDINGS: By combining microarray data and conventional approaches, it is becoming clear that the M1 polarization program is associated with gastrointestinal infections (e.g. typhoid fever and Helicobacter pylori gastritis) and active tuberculosis. An M2 signature is observed in lepromatous leprosy, Whipple's disease, and localized infections (keratitis, chronic rhinosinusitis). However, these findings could not be predicted from the analysis of the M1/M2 programs of macrophages stimulated in vitro. SUMMARY: The reappraisal of macrophage polarization by high-throughput methods is critical to understanding the role of macrophage polarization in infectious diseases. Only the identification of individual profiles will support promising therapeutic approaches based on target determination.