Constant replenishment from circulating monocytes maintains the macrophage pool in the intestine of adult mice

Abstract

The paradigm that resident macrophages in steady-state tissues are derived from embryonic precursors has never been investigated in the intestine, which contains the largest pool of macrophages. Using fate mapping models and monocytopenic mice, together with bone marrow chimeric and parabiotic models, we show that embryonic precursors seeded the intestinal mucosa and demonstrated extensive in situ proliferation in the neonatal period. However these cells did not persist in adult intestine. Instead, they were replaced around the time of weaning by the CCR2-dependent influx of Ly6Chi monocytes that differentiated locally into mature, anti-inflammatory macrophages. This process was driven largely by the microbiota and had to be continued throughout adult life to maintain a normal intestinal macrophage pool.

Phenotypic and Functional Plasticity of Murine Intestinal NKp46+ Group 3 Innate Lymphoid Cells

“…The addition of TGF-b accelerated GFP downregulation in CD49a + GFP + cells cultured on OP9, but not on OP9-DL1, cells (Fig. 4D) (35), whereas cellular partners that emerge after birth, such as monocyte-derived CX3CR1 + macrophages, may stabilize NKp46 expression by providing Notch ligands (36). To balance their function, TGF-b might dampen an ILC3 proinflammatory program that is dependent on NKp46 expression.…”

Microbiote intestinal et développement du système immunitaire

“…Néanmoins, le dialogue entre hôtes et bactéries, initié lors de la colonisation intestinale à la naissance, est indispensable à la maturation de la l'intestin où ils acquièrent une activité très efficace de phagocytose tout en devenant producteurs d'IL-10 (interleukine 10). Cette cytokine anti-inflammatoire, clé dans le maintien de l'homéostasie intestinale [9,10], contribue à leur propre conditionnement et les rend tolérants aux signaux pro-inflammatoires induits par les motifs bactériens [8]. Ces macrophages peuvent ainsi éliminer les bactéries qui franchissent l'épithélium sans provoquer de réponse inflammatoire délétère.…”

“…Ces macrophages peuvent ainsi éliminer les bactéries qui franchissent l'épithélium sans provoquer de réponse inflammatoire délétère. Néanmoins, en cas d'infection, des monocytes sanguins non conditionnés, capables de produire de grandes quantités de cytokines inflammatoires (TNF [tumor necrosis factor alpha] et IL-1) en réponse aux signaux microbiens, sont recrutés localement pour participer à l'élimination des bactéries potentiellement pathogènes [8]. En complément, les éosinophiles sont nombreux même dans l'intestin normal où leur rôle reste mal compris.…”

“…Les phagocytes Parmi les phagocytes, les macrophages CD11b + CX 3 CR1 hi (C-X3-C motif chemokine receptor 1) sont, en situation physiologique, les cellules les plus nombreuses dans le chorion [8]. Renouvelés en permanence à partir des monocytes sanguins, ils se différencient dans giés de l'initiation des réponses immunes adaptatives.…”

Maturation Phenotype of Peripheral Blood Monocyte/Macrophage After Stimulation with Lipopolysaccharides in Irritable Bowel Syndrome

“…14 The maturation process of monocytes into macrophages that takes place in the intestine is carried out by a continuous flow of monocytes coming from the blood stream. 15 This monocyte recruitment provides a constant intestinal replenishment of macrophage populations that gradually mature in a cascade-like manner until they reach the level of resident macrophages. 16,17 Our hypothesis was that patients with IBS may show an alteration in the maturation cascade of monocytes into macrophages in response to bacterial components in charge of triggering this disorder.…”