Revisiting the protective and pathogenic roles of neutrophils: Ly-6G is key!

The physiological and pathophysiological roles of neutrophils in immune homeostasis and disease have been investigated extensively by way of anti-Gr-1 mAb-mediated depletion experiments; however, the ability of the anti-Gr-1 mAb to specifically deplete neutrophils has long been questioned and it is now known that this mAb, which binds Ly6C and Ly6G, is also able to deplete monocytes and subsets of CD8(+) T cells. This, therefore, casts doubt on the previous conclusions regarding the role of neutrophils drawn from studies using this mAb. Another mAb, which targets Ly6G only, has recently been shown to deplete neutrophils specifically and a study by Carr et al. (Eur. J. Immunol. 2011. 41: 2666-2676) in this issue of the European Journal of Immunology utilizes this Ly-6G mAb to reveal the precise role of neutrophils during Listeria monocytogenes (LM) infection. Carr et al. find that monocytes/macrophages, rather than neutrophils, dominate the initial control of LM growth in the spleen, whereas neutrophils in the liver are key for host resistance to LM infection. These data suggest that the previously reported protective or pathogenic roles of neutrophils in disease models need to be reconsidered through anti-Ly6G mAb-mediated depletion experiments.