Molecular Machinations: Chemokine Signals in Host-Pathogen Interactions

Abstract

Chemokines and their G-protein-coupled receptors represent an ancient and complex system of cellular communication participating in growth, development, homeostasis and immunity. Chemokine production has been detected in virtually every microbial infection examined; however, the precise role of chemokines is still far from clear. In most cases they appear to promote host resistance by mobilizing leukocytes and activating immune functions that kill, expel, or sequester pathogens. In other cases, the chemokine system has been pirated by pathogens, especially protozoa and viruses, which have exploited host chemokine receptors as modes of cellular invasion or developed chemokine mimics and binding proteins that act as antagonists or inappropriate agonists. Understanding microbial mechanisms of chemokine evasion will potentially lead to novel antimicrobial and anti-inflammatory therapeutic agents

Lipocalin-2 Is a Chemokine Inducer in the Central Nervous System

“…For instance, astrocyte migration has been demonstrated, in vitro, in response to CCL2, CXCL10, and CXCL12 (30,31,59). Although the expression of chemokines is commonly induced by inflammatory cytokines and pathogens (60), less is known about other molecular mediators that induce chemokine expression in the CNS. The expression of chemokines is regulated by many stimulatory and inhibitory factors, such as Toll-like receptor-3, UDP, TGF-␤, 17␤-estradiol, and HIV-1 glycoprotein 120 in the CNS (19 -21, 61-65).…”

Herpes Simplex Virus and the Chemokines That Mediate the Inflammation

“…The expression profile of CCL5 and CXCL10 suggest the resident population generates most if not all of the CXCL10 within the first 24 hr post infection whereas CCL5 is produced principally by resident cells but may also be provided by the infiltrating PMNs that are found within the stroma 24 hr post infection [Carr et al, submitted]. It is likely that as the infection spreads over the next several hours, chemokines generated including CCL2, CCL5, CXCL1, CXCL2, CXCL9, and CXCL10 are produced by multiple sources including the resident fibroblasts, epithelial, and endothelial cells as well as infiltrating PMNs, macrophages, NK cells, and dendritic cells [11,25,82,87,100]. Collectively, the initial cascade of chemokine expression is complex but may be divided into two principal pathways involving CXCL10 and IL-6 (Fig.…”

“…While trauma to the cornea in the form of scarification induced the expression, continued expression of CCL2, CCL5, and CXCL10 were noted out to 72 hr post infection whereas other chemokine mRNA levels precipitously dropped in both BALB/c and outbred ICR mice [14,90]. Of the chemokines noted above, CXCL1 and CXCL2 specifically target neutrophils principally through the receptor, CXCR2 [11,82,99,104]. Neutralization of CXCL2 with antibody leads to a reduction in PMN infiltration into the cornea [54,104].…”

“…Since CCL3 targets monocytes, T cells, natural killer (NK) cells, basophils, eosinophils, dendritic cells (DCs), and hematopoietic progenitors [11,12,82], it is currently unknown what events transpire to recruit the subsequent wave of cells. However, CCL3 is central to the effect since neutralizing this chemokine with antibody or suppressing expression with IL-10 reduces leukocyte recruitment into the cornea [99].…”

Phylogenetic analysis of Gansu sheeppox virus isolates based on P32, GPCR, and RPO30 genes

“…Because of the size difference of P32 between SPPV and GTPV, they can be distinguished by sequence comparison (Tian et al, 2010). GPCR, which is involved in defense against the aggressive assault executed by host inflammatory responses (Chensue, 2001;Seet and McFadden, 2002), has been used for differential diagnosis of SPPV, GTPV, and LSDV (Le Goff et al, 2009;Lamien et al, 2011b). The RPO30 gene, a homolog of the vaccinia virus E4L gene, encodes a 30-kDa DNA-dependent RNA polymerase subunit (Ahn et al, 1990;Tulman et al, 2002).…”