Monocyte-Mediated Defense Against Microbial Pathogens

Abstract

Circulating blood monocytes supply peripheral tissues with macrophage and dendritic cell (DC) precursors and, in the setting of infection, also contribute directly to immune defense against microbial pathogens. In humans and mice, monocytes are divided into two major subsets that either specifically traffic into inflamed tissues or, in the absence of overt inflammation, constitutively maintain tissue macrophage/DC populations. Inflammatory monocytes respond rapidly to microbial stimuli by secreting cytokines and antimicrobial factors, express the CCR2 chemokine receptor, and traffic to sites of microbial infection in response to monocyte chemoattractant protein (MCP)-1 (CCL2) secretion. In murine models, CCR2-mediated monocyte recruitment is essential for defense against Listeria monocytogenes, Mycobacterium tuberculosis, Toxoplasma gondii, and Cryptococcus neoformans infection, implicating inflammatory monocytes in defense against bacterial, protozoal, and fungal pathogens. Recent studies indicate that inflammatory monocyte recruitment to sites of infection is complex, involving CCR2-mediated emigration of monocytes from the bone marrow into the bloodstream, followed by trafficking into infected tissues. The in vivo mechanisms that promote chemokine secretion, monocyte differentiation and trafficking, and finally monocyte-mediated microbial killing remain active and important areas of investigation.

Migration of Fibrocytes in Fibrogenic Liver Injury

“…They expressed CD11b (82% Ϯ 7%), Ly-6C (75% Ϯ 6%), F4/80 (25% Ϯ 5%), and CD115 (53% Ϯ 6%; Figure 4, A and B), low levels of CD14, and CD68 ( Figure 4D), resembling CD11b ϩ Ly6c ϩ CCR2 ϩ CD115 ϩ monocytes. 20 Similar to mature fibrocytes, 18 CD45 ϩ Col ϩ cells expressed chemokine receptors CCR1 (15% Ϯ 5%) and CCR2 (18% Ϯ 4%; Figure 4A), major histocompatibility complex class II (18% Ϯ 10%), and hematopoietic markers CD34, CD133, CD105, and Thy1.1 ( Figure 4, B and 4D). 20 To test whether BM CD45 ϩ Col ϩ cells possess fibrocyte features, CD45 ϩ Col ϩ cells were purified from BM by cell sorting 4 for double-positive CD45 ϩ and Col-GFP ϩ cells ( Figure 5A) and characterized by structure and gene expression.…”

“…20 Similar to mature fibrocytes, 18 CD45 ϩ Col ϩ cells expressed chemokine receptors CCR1 (15% Ϯ 5%) and CCR2 (18% Ϯ 4%; Figure 4A), major histocompatibility complex class II (18% Ϯ 10%), and hematopoietic markers CD34, CD133, CD105, and Thy1.1 ( Figure 4, B and 4D). 20 To test whether BM CD45 ϩ Col ϩ cells possess fibrocyte features, CD45 ϩ Col ϩ cells were purified from BM by cell sorting 4 for double-positive CD45 ϩ and Col-GFP ϩ cells ( Figure 5A) and characterized by structure and gene expression. Expression of collagen type I in purified BM CD45 ϩ Col ϩ cells was confirmed by positive staining with anti-collagen type I antibody ( Figure 5A) but not with isotype-matched control antibody (data not shown).…”

Concomitant activation of P2Y2 and P2Y6 receptors on monocytes is required for TLR1/2‐induced neutrophil migration by regulating IL‐8 secretion

“…Monocytes play an important role in immune defences against invading bacteria and viruses via TLR activation [1]. TLR recognize highly conserved structural motifs expressed by microbes called PAMP.…”

“…P2 receptors are divided into two subfamilies: the G-protein-coupled receptors (P2Y 1,2,4,6,[11][12][13][14] ) and the ligand-gated ion channels (P2X 1-7 ). The P2Y subtypes differ in their selectivity toward adenine (ATP, ADP) and uracil nucleotides (UTP, UDP) while all P2X receptors are activated by ATP [10,11].…”

“…The P2Y subtypes differ in their selectivity toward adenine (ATP, ADP) and uracil nucleotides (UTP, UDP) while all P2X receptors are activated by ATP [10,11]. Human primary monocytes and monocytic cell lines (THP-1 and U937) express the mRNA of various P2 receptors of which P2X 1,7 and P2Y 2,6,11 are common to all these cells [12,13]. There is growing evidence indicating that P2 receptors mediate some important proinflammatory responses activated by the stimulation of monocytes/macrophages with PAMP.…”