TY - JOUR
T1 - Alternatively activated macrophages in infection and autoimmunity
AU - Fairweather, De Lisa
AU - Cihakova, Daniela
N1 - Funding Information:
Work discussed in this review was supported by NIH R01 grants HL087033 (D.F.) and HL67290, HL70729 and a Fellowship Grant from the Myocarditis Foundation (D.C.).
PY - 2009/11
Y1 - 2009/11
N2 - Macrophages are innate immune cells that play an important role in activation of the immune response and wound healing. Pathogens that require T helper-type 2 (Th2) responses for effective clearance, such as parasitic worms, are strong inducers of alternatively activated or M2 macrophages. However, infections such as bacteria and viruses that require Th1-type responses may induce M2 as a strategy to evade the immune system. M2 are particularly efficient at scavenging self tissues following injury through receptors like the mannose receptor and scavenger receptor-A. Thus, M2 may increase autoimmune disease by presenting self tissue to T cells. M2 may also exacerbate immune complex (IC)-mediated pathology and fibrosis, a hallmark of autoimmune disease in women, due to the release of profibrotic factors such as interleukin-1β, transforming growth factor-β, fibronectin and matrix metalloproteinases. We have found that M2 comprise anywhere from 30% to 70% of the infiltrate during acute viral or experimental autoimmune myocarditis, and shifts in M2 populations correlate with increased IC deposition, fibrosis and chronic autoimmune pathology. Thus, women may be at an increased risk of M2-mediated autoimmunity due to estrogen's ability to increase Th2 responses.
AB - Macrophages are innate immune cells that play an important role in activation of the immune response and wound healing. Pathogens that require T helper-type 2 (Th2) responses for effective clearance, such as parasitic worms, are strong inducers of alternatively activated or M2 macrophages. However, infections such as bacteria and viruses that require Th1-type responses may induce M2 as a strategy to evade the immune system. M2 are particularly efficient at scavenging self tissues following injury through receptors like the mannose receptor and scavenger receptor-A. Thus, M2 may increase autoimmune disease by presenting self tissue to T cells. M2 may also exacerbate immune complex (IC)-mediated pathology and fibrosis, a hallmark of autoimmune disease in women, due to the release of profibrotic factors such as interleukin-1β, transforming growth factor-β, fibronectin and matrix metalloproteinases. We have found that M2 comprise anywhere from 30% to 70% of the infiltrate during acute viral or experimental autoimmune myocarditis, and shifts in M2 populations correlate with increased IC deposition, fibrosis and chronic autoimmune pathology. Thus, women may be at an increased risk of M2-mediated autoimmunity due to estrogen's ability to increase Th2 responses.
KW - Autoimmunity
KW - Complement
KW - Cytokines
KW - Infection
KW - Macrophage
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U2 - 10.1016/j.jaut.2009.09.012
DO - 10.1016/j.jaut.2009.09.012
M3 - Article
C2 - 19819674
AN - SCOPUS:71649091697
SN - 0896-8411
VL - 33
SP - 222
EP - 230
JO - Journal of Autoimmunity
JF - Journal of Autoimmunity
IS - 3-4
ER -