Distinct Differentiation Potential of Blood Monocyte Subsets in the Lung

Abstract

Peripheral blood monocytes are a population of circulating mononuclear phagocytes that harbor potential to differentiate into macrophages and dendritic cells. As in humans, monocytes in the mouse comprise two phenotypically distinct subsets that are Gr1 high CX 3 CR1 int and Gr1 low CX 3 CR1 high , respectively. The question remains whether these populations contribute differentially to the generation of peripheral mononuclear phagocytes. In this study, we track the fate of adoptively transferred, fractionated monocyte subsets in the lung of recipient mice. We show that under inflammatory and noninflammatory conditions, both monocyte subsets give rise to pulmonary dendritic cells. In contrast, under the conditions studied, only Gr1 low CX 3 CR1 high monocytes, but not Gr1 high CX 3 CR1 int cells, had the potential to differentiate into lung macrophages. However, Gr1 high CX 3 CR1 int monocytes could acquire this potential upon conversion into Gr1 low CX 3 CR1 high cells. Our results therefore indicate an intrinsic dichotomy in the differentiation potential of the two main blood monocyte subsets.

Modulation of pulmonary DC function by vaccine‐encoded GM‐CSF enhances protective immunity against Mycobacterium tuberculosis infection

“…2A). These cells were designated as conventional myeloid DC and alveolar macrophages, respectively [20,21]. The total number of MHC II hi CD11c hi and MHC II int CD11c hi cells was significantly higher in the lungs of BCG:GM-CSF-vaccinated compared with BCGvaccinated mice at days 14, 28 and 56 ( Fig.…”

“…The increased number of these cells may be explained by our observed effect of vaccine-derived GM-CSF on APC expansion in situ, particularly alveolar macrophages [28] and lung-resident and MLN migratory DC [20,21]. The increased percentage and number of these MHC II hi migratory MLN DC suggest that in the presence of an inflammatory stimulus it is mainly these cells which home to the draining MLN, presenting antigen and secreting IL-12 at the draining site to induce the proliferation of antigen-specific CD4 1 Th1 (Fig.…”

Impaired dendritic cell differentiation of CD16‐positive monocytes in tuberculosis: Role of p38 MAPK

“…In particular, it is known that in lungs DCs develop from both Ly6C high and Ly6C low Mos, while M s originate from Ly6C low Mos, which resemble the human CD16 + subset [41]. Despite this, whether the differentiation fates described in mice Mo subsets resemble the ones in humans remains unknown.…”

Origin and functional specializations of DC subsets in the lung

“…In many mouse models of lung immunity, broncho-alveolar lavage is performed. The recovered lavage contains both CD11b 1 and CD11b À cDC, but it is unclear at present whether these derive from large airways or parenchyma [11,12]. Some DC also patrol the vessel wall of the pulmonary arterial vasculature, and these are mainly CX3CR1 1 CD11b 1 cells [13].…”