Alternatively activated macrophages in helminth infections

Kreider, Timothy; Anthony, Robert M.; Urban, Joseph F.; Gause, William C.

doi:10.1016/j.coi.2007.07.002

Cited by 318 publications

(284 citation statements)

References 50 publications

Supporting

Mentioning

271

Contrasting

Unclassified

Order By: Relevance

“…Therefore, it is not surprising that mechanisms to repair damaged host tissues would be an integral part of an appropriate immune response against helminths [112]. This concept of tissue repair is in line with the observation that alternatively activated macrophages, which play a crucial role in type 2-associated processes such as fibrosis [113], are highly reminiscent of the macrophages that are required for wound healing and which are found in lesions caused by non-infectious injuries [114]. On this basis, one could hypothesize that not only are tissue repair mechanisms part of the Th2 response seen during helminth infections, but that tissue damage and cellular stress inflicted by the parasites are actually the triggers for the induction of type 2 responses.…”

Section: Why Th2 and Treg?mentioning

confidence: 61%

Helminths and dendritic cells: Sensing and regulating via pattern recognition receptors, Th2 and Treg responses

et al. 2010

View full text Add to dashboard Cite

The classical reaction of the host to helminth infections is the induction of Th2 immune responses with a regulatory component. DC, as central players in the induction and maintenance of immune responses, play a prominent role in both these processes, and in recent years considerable progress has been made in elucidating the mechanisms behind the interplay between DC and helminths. It is becoming increasingly clear that helminths modulate DC function not only via direct interactions but also indirectly via host-derived cues. Furthermore, while studies have until recently focused on receptor signalingmediated DC modulation by helminths, evidence is emerging that DC may also respond to helminth infections by sensing stress signals or tissue damage inflicted by the worms or their products. Here, we will discuss these new insights and will link them to the origin and importance of Th2 and regulatory immune responses with respect to the survival of both parasite and host.Key words: DC . Helminth . Th cell polarization . Tissue damage IntroductionThe classical reaction of the host to helminth infections is the induction of Th2 responses. The induction of Th2 immunity has been shown to be important for resistance to helminth infections in various model systems; however, despite induction of a Th2 response, total clearance of the parasites rarely occurs in man (reviewed in [1,2]). This implies that helminths have evolved strategies, such as evasion or suppression of the host immune response that prevent their expulsion and permit their long-term survival. The immune modulatory effects are thought to arise from the helminth's capacity to exploit the host's own system of immune regulation, which is normally crucial for the maintenance of immune homeostasis and self tolerance. In this respect, the induction of Treg has been shown to be one of the most common mechanisms that restrains immune responses against the parasite while also preventing excessive inflammation and tissue damage inflicted by the worms (reviewed in [2,3]). Therefore, it is not surprising that among the variety of mechanisms developed by helminths to influence host immune responses, modulation of DC as pivotal players in the initiation and polarization of adaptive immune responses, including Treg modulation, may have a particularly important role (reviewed in [2,4,5] ) carbohydrate epitope found in schistosoma soluble egg antigens (SEA), has been implicated in TLR4-dependent priming of Th2 responses via DC [9]. However, SEA is also known to be capable of modulating DC for Th2 priming in the absence of TLR signaling [10]. Furthermore, phosphatidylserine (PS) lipids derived from schistosomes and ascaris worms, which carry TLR2-activating molecules, have been shown to promote Th2 responses via DC, but this is not TLR2 dependent [11], whereas monoacetylated PS lipids from schistosomes were found to specifically instruct DC to preferentially induce IL-10-producing Treg in a TLR2-dependent fashion [12]. Although TLR2 does not seem to be essential for Th2 polar...

show abstract

Section: Why Th2 and Treg?mentioning

confidence: 61%

Helminths and dendritic cells: Sensing and regulating via pattern recognition receptors, Th2 and Treg responses

et al. 2010

View full text Add to dashboard Cite

show abstract

“…Secondly, since HS and heparin are physiological ligands to Ym1 (Chang et al, 2001), it may be speculated that changes in HS turnover affect Ym1 aggregation and crystallization. Finally, Ym1 is selectively expressed by alveolar macrophages and immature neutrophils under normal conditions (Nio et al, 2004) and is only expressed by peritoneal macrophages upon LPS-stimulation (Hung et al, 2002) or differentiation into alternatively activated macrophages (Kreider et al, 2007;Rauh et al, 2005). The selective expression of Ym1 in alveolar, but not peritoneal macrophages is well in line with the appearance of granule-like structures only in the former cell type.…”

Section: Discussionmentioning

confidence: 97%

Accumulation of Ym1 and formation of intracellular crystalline bodies in alveolar macrophages lacking heparanase

Waern

Jia

Pejler

et al. 2010

Molecular Immunology

View full text Add to dashboard Cite

Heparanase is a heparan sulfate (HS) degrading endoglucuronidase that has been implicated in cell migration and inflammatory conditions. Here we used mice deficient of heparanase (Hpse -/-) to study the impact of heparanase on airway leukocytes. Normal numbers of macrophages and lymphocytes were present in bronchoalveolar lavage fluid of Hpse-/-mice, indicating that heparanase is not essential for proper homing of leukocytes to airways. While lymphocytes fromHpse -/-mice displayed normal morphology, Hpse -/-alveolar macrophages showed a striking, age-dependent appearance of granule-like structures in the cytoplasm.Transmission electron microscopy revealed that these structures corresponded to membrane-enclosed crystalline bodies that closely resembled the intracellular crystals known to be formed by the HS-binding protein Ym1, suggesting that heparanase deficiency is associated with intracellular Ym1 deposition. Indeed, applying immunocytochemistry, we found markedly higher levels of intracellular

show abstract

“…Two hypothesis can be made: Treatment of macrophages by GC induce their differentiation as "alternatively activated macrophages". These alternatively activated macrophages are anti-inflammatory and pro-fibrotic, and induce wound repair [40]. In this context, production of an enzyme by alternatively activated macrophages, which is critical for collagen maturation, but quite limiting and poorly inducible in fibroblasts, makes sense and would favor collagen and extracellular matrix accumulation.…”

Section: Discussionmentioning

confidence: 99%

Tissue-specific induction of ADAMTS2 in monocytes and macrophages by glucocorticoids

et al. 2007

View full text Add to dashboard Cite

The regulated expression of ADAMTS2 (a disintegrin and metalloproteinase with thrombospondin motifs), a secreted metalloproteinase involved in the processing of procollagen to collagen, was studied in peripheral blood mononuclear cells (PBMC). Stimulation with glucocorticoids (GC) resulted in a pronounced dose-and timedependent increase of ADAMTS2 mRNA levels in PBMC. The increase of ADAMTS2 expression was specific for CD14++ monocytes (440-fold) and alveolar macrophages (200-fold), whereas CD3+ (T lymphocytes), phytohemagglutinin-activated CD3+ (T lymphocytes), and CD19+ (B lymphocytes) showed no significant changes in ADAMTS2 mRNA after GC treatment. Treatment of monocyte-derived macrophages (MDM) with GC also resulted in an increase of ADAMTS2 protein in the culture tissue media. Using the GC analog RU486, GC-mediated induction of ADAMTS2 mRNA was blocked, implicating that GC acts specifically via the GCreceptor. In agreement with findings in blood monocytes, cell lines of the monocytic lineage (MM6, THP-1) showed significant GC-induced significant increases in ADAMTS2 mRNA, while in epithelial cells (A549, Calu-3, Colo320, BT-20) and fibroblast (MRC-5, WI-38, and two NHDF-c cell types from adult cheek and upper arm), they showed no or little responsiveness to GC. As macrophages have important functions in immune defense and tissue homeostasis, these findings suggest that GC-mediated specific induction of ADAMTS2 in these cells may play a crucial role in the resolution of inflammation and wound repair.

show abstract

Alternatively activated macrophages in helminth infections

Cited by 318 publications

References 50 publications

Helminths and dendritic cells: Sensing and regulating via pattern recognition receptors, Th2 and Treg responses

Helminths and dendritic cells: Sensing and regulating via pattern recognition receptors, Th2 and Treg responses

Accumulation of Ym1 and formation of intracellular crystalline bodies in alveolar macrophages lacking heparanase

Tissue-specific induction of ADAMTS2 in monocytes and macrophages by glucocorticoids

Contact Info

Product

Resources

About