CC Chemokine Receptor 4 Contributes to Innate NK and Chronic Stage T Helper Cell Recall Responses during Mycobacterium bovis Infection

Abstract

Cysteine-cysteinyl chemokine receptor 4 (CCR4) is expressed by a variety of T-cell subsets and leukocytes. This study examined the participation of CCR4 in response to

Chemokines shape the immune responses to tuberculosis

“…Consistent with these data, instillation of CCR4KO mice with PPD coated beads in the lung resulted in impaired granuloma formation and exhibited reduced IFNγ production at the lesion site [34]. In addition, in a model of acute M.bovis pulmonary infection, CCR4KO mice exhibited higher susceptibility with increased bacterial burden in the lung early in infection [42]. The increased susceptibility in CCR4KO mice also coincided with formation of smaller granulomas and reduced accumulation of innate NKT cells as well as defects in late stage CD4 + T cells that produced the cytokines, IFNγ and IL-17 [42].…”

“…In addition, in a model of acute M.bovis pulmonary infection, CCR4KO mice exhibited higher susceptibility with increased bacterial burden in the lung early in infection [42]. The increased susceptibility in CCR4KO mice also coincided with formation of smaller granulomas and reduced accumulation of innate NKT cells as well as defects in late stage CD4 + T cells that produced the cytokines, IFNγ and IL-17 [42]. Although these studies indicate a potential role of CCR4 in immunity to mycobacterial infections, following infection with low doses of aerosolized Mtb , CCR4KO mice are not more susceptible and exhibit comparable bacterial burden in the lungs as wild type Mtb -infected mice ( Slight and Khader, unpublished findings ).…”

Chemokine receptors and their therapeutic opportunities in diseased lung: Far beyond leukocyte trafficking

“…Obviously, the role of this chemokine receptor depends upon the types of microorganisms infected in the lung. Mice deficient in CCR4, when challenged with M. bovis, showed reduced inflammation and delayed bacterial clearance (149). On the other hand, the deficiency of CCR6 in mice resulted in more severe infection and higher mortality rate and lung fungal burden when challenged with A. fumigatus (123).…”

CCR4 contributes to the pathogenesis of experimental autoimmune encephalomyelitis by regulating inflammatory macrophage function

“…While CCR4 is often associated with Th2 and Treg populations (Imai et al, 1999; Lee et al, 2005), a variety of cell types express this receptor (Abi-Younes et al, 2001; Meyer et al, 2007; Stolberg et al, 2011). Importantly, there is a growing body of literature describing a role for CCR4 in iMϕ function (Dogan et al, 2011; Ness et al, 2006b; Trujillo et al, 2008; Yogo et al, 2009).…”