scholarly journals Chronic Helminth Infection Induces Alternatively Activated Macrophages Expressing High Levels of CCR5 with Low Interleukin-12 Production and Th2-Biasing Ability

2002 ◽  
Vol 70 (7) ◽  
pp. 3656-3664 ◽  
Author(s):  
Miriam Rodríguez-Sosa ◽  
Abhay R. Satoskar ◽  
Rodrigo Calderón ◽  
Lorena Gomez-Garcia ◽  
Rafael Saavedra ◽  
...  
Keyword(s):  
T Cells ◽  
Cd4 T Cells ◽  
Interleukin 12 ◽  
Prostaglandin E ◽  
Activated Macrophages ◽  
Chronic Infections ◽  
Alternatively Activated Macrophages ◽  
Acute Infections ◽  
Helminth Infections ◽  
Alternatively Activated

ABSTRACT Helminth infections induce Th2-type biased immune responses. Although the mechanisms involved in this phenomenon are not yet clearly defined, antigen-presenting cells (APC) could play an important role in this process. Here, we have used peritoneal macrophages (F4/80+) recruited at different times after challenge with Taenia crassiceps as APC and tested their ability to regulate Th1/Th2 differentiation. Macrophages from acute infections produced high levels of interleukin-12 (IL-12) and nitric oxide (NO), paralleled with low levels of IL-6 and prostaglandin E2 (PGE2) and with the ability to induce strong antigen-specific CD4+ T-cell proliferation in response to nonrelated antigens. In contrast, macrophages from chronic infections produced higher levels of IL-6 and PGE2 and had suppressed production of IL-12 and NO, associated with a poor ability to induce antigen-specific proliferation in CD4+ T cells. Failure to induce proliferation was not due to a deficient expression of accessory molecules, since major histocompatibility complex class II, CD40, and B7-2 were up-regulated, together with CD23 and CCR5 as infection progressed. These macrophages from chronic infections were able to bias CD4+ T cells to produce IL-4 but not gamma interferon (IFN-γ), contrary to macrophages from acute infections. Blockade of B7-2 and IL-6 and inhibition of PGE2 failed to restore the proliferative response in CD4+ T cells. Furthermore, studies using STAT6−/− mice revealed that STAT6-mediated signaling was essential for the expansion of these alternatively activated macrophages. These data demonstrate that helminth infections can induce different macrophage populations that have Th2-biasing properties.

scholarly journals Similarity and Diversity in Macrophage Activation by Nematodes, Trematodes, and Cestodes

2010 ◽  
Vol 2010 ◽  
pp. 1-14 ◽  
Author(s):  
Stephen J. Jenkins ◽  
Judith E. Allen
Keyword(s):  
Macrophage Activation ◽  
Helminth Infection ◽  
Current Knowledge ◽  
Host Tissue ◽  
Macrophage Phenotype ◽  
Activated Macrophages ◽  
Alternatively Activated Macrophages ◽  
Helminth Infections ◽  
Host Metabolism ◽  
Alternatively Activated

This review summarizes current knowledge of macrophages in helminth infections, with a focus not only on delineating the striking similarities in macrophage phenotype between diverse infections but also on highlighting the differences. Findings from many different labs illustrate that macrophages in helminth infection can act as anti-parasite effectors but can also act as powerful immune suppressors. The specific role for their alternative (Th2-mediated) activation in helminth killing or expulsion versus immune regulation remains to be determined. Meanwhile, the rapid growth in knowledge of alternatively activated macrophages will require an even more expansive view of their potential functions to include repair of host tissue and regulation of host metabolism.

scholarly journals Alternatively activated macrophages in helminth infections

2007 ◽  
Vol 19 (4) ◽  
pp. 448-453 ◽  
Author(s):  
Timothy Kreider ◽  
Robert M. Anthony ◽  
Joseph F. Urban ◽  
William C. Gause
Keyword(s):  
Activated Macrophages ◽  
Alternatively Activated Macrophages ◽  
Helminth Infections ◽  
Alternatively Activated

scholarly journals Taenia crassiceps Antigens Control Experimental Type 1 Diabetes by Inducing Alternatively Activated Macrophages

2017 ◽  
Vol 2017 ◽  
pp. 1-15 ◽  
Author(s):  
Arlett Espinoza-Jiménez ◽  
Roberto De Haro ◽  
Luis I. Terrazas
Keyword(s):  
Type 1 Diabetes ◽  
Suppressor Cells ◽  
Activated Macrophages ◽  
Taenia Crassiceps ◽  
Alternatively Activated Macrophages ◽  
Helminth Infections ◽  
Experimental Type ◽  
Classically Activated Macrophages ◽  
Alternatively Activated

Type 1 diabetes (T1D) is an autoimmune disease caused by the selective destruction of the pancreatic β-cells, causing inability to produce insulin. Proinflammatory cytokines such as IL-1β, IL-6, TNF-α, IFN-γ, IL-12, IL-17, and NO can be released by CD4 and CD8+ lymphocytes as well as by classically activated macrophages (CAMϕs), which are important in the development of T1D. Helminth infections have been shown to prevent T1D, mainly through Th2-biased responses and increased recruitment of regulatory cell populations. Previously, we have shown that Taenia crassiceps infection in mice significantly reduces hyperglycemia, insulitis, and the incidence of T1D. In this study, we determined whether T. crassiceps-derived products such as soluble (TcS) or excreted/secreted (TcES) antigens might have a beneficial influence on the development of experimental T1D. Treatment with different doses before or after induction of T1D was analyzed. Mice that were pretreated with TcS were unable to develop T1D, whereas those receiving TcES early after T1D induction displayed significantly reduced insulitis and hyperglycemia along with increased recruitment of alternatively activated macrophages (AAMϕs) and myeloid-derived suppressor cells (MDSCs). Finally, we examined the modulatory role of AAMϕs on T1D by depleting macrophages with clodronate-loaded liposomes, demonstrating that AAMϕs are key cells in T1D regulation.

CD28 loss in senescent CD4+ T cells: reversal by interleukin-12 stimulation

Blood ◽  
2003 ◽  
Vol 101 (9) ◽  
pp. 3543-3549 ◽  
Author(s):  
Kenneth J. Warrington ◽  
Abbe N. Vallejo ◽  
Cornelia M. Weyand ◽  
Jörg J. Goronzy
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd4 T Cells ◽  
Costimulatory Molecule ◽  
Cd40 Ligand ◽  
Interleukin 12 ◽  
Chronic Infections ◽  
Replicative Stress ◽  
Cell Clones ◽  
Factor Α

CD28 is the quintessential costimulatory molecule expressed on CD4+ and CD8+ T cells. During chronic infections and the normal aging process, CD28 expression is lost, compromising the functional activity of T cells. CD28 loss is promoted by replicative stress, particularly in the presence of tumor necrosis factor–α, owing to an inoperative CD28 initiator element. It is currently unknown whether CD28 loss is irreversible. The present study examined cytokines for their ability to reinduce CD28 expression. CD4+CD28null T cells constitutively expressed interleukin-12 (IL-12) α and β receptors, which were functional and allowed for the up-regulation of the signal transducer and activator of transcription–4 (STAT-4)–dependent gene CD161. Costimulation of the T-cell and IL-12 receptors induced the transcription of CD28 in approximately 50% of CD4+CD28null T-cell clones and lines. IL-12 by itself did not restore CD28 expression. Up-regulation of CD28 after IL-12 exposure correlated with the reassembly of the CD28–initiator protein complex. The re-expressed CD28 was functional and restored the ability of CD4+CD28null T cells to express CD25 and CD40 ligand. Our data suggest that IL-12 may, in part, functionally rescue senescent CD4+ T cells.

scholarly journals Alternatively activated macrophages inhibit T-cell proliferation by Stat6-dependent expression of PD-L2

Blood ◽  
2010 ◽  
Vol 116 (17) ◽  
pp. 3311-3320 ◽  
Author(s):  
Silke Huber ◽  
Reinhard Hoffmann ◽  
Femke Muskens ◽  
David Voehringer
Keyword(s):  
Cell Proliferation ◽  
T Cells ◽  
T Cell ◽  
Inhibitory Activity ◽  
Th2 Cells ◽  
T Cell Proliferation ◽  
Activated Macrophages ◽  
Alternatively Activated Macrophages ◽  
Deficient Mice ◽  
Alternatively Activated

Abstract Alternatively activated macrophages (AAM) accumulate in tissues during Th2-associated immune responses like helminth infections and allergic disorders. These cells differentiate in response to interleukin 4 (IL-4)/IL-13–mediated activation of Stat6 and possess potent inhibitory activity against T cells. The molecular mechanism that leads to T-cell suppression remains unclear and could involve soluble factors or inhibitory ligands. Microarray analysis revealed that the inhibitory ligand, programmed death ligand 2 (PD-L2) was strongly induced by IL-4 in macrophages from wild-type but not Stat6-deficient mice. PD-L2 expression correlated with other established markers for AAM-like Relm-α/Fizz1, arginase1, or Ym1 and thereby serves as useful surface marker to identify and isolate AAM from tissues. Antibodies against PD-L2 blocked the inhibitory activity of AAM and retroviral expression of PD-L2 in macrophages from Stat6−/− mice was sufficient to inhibit T-cell proliferation, which demonstrates that PD-L2 mediates potent and nonredundant inhibition of T cells independently of other Stat6-regulated genes. Infection of conditional IL-4/IL-13–deficient mice with the helminth Nippostrongylus brasiliensis further showed that PD-L2 expression was dependent on IL-4/IL-13 from Th2 cells. In vivo blockade of PD-L2 during N brasiliensis infection caused an enhanced Th2 response in the lung, indicating that AAM inhibit Th2 cells by expression of PD-L2.

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