Frontiers in immunology
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M1 and M2 macrophage-type responses kill or repair in vivo. The unique ability of macrophages to make these polar opposite type of responses provides primary host protection and maintains tissue homeostasis throughout the animal kingdom. In humans and other higher animals, M1 and M2-type macrophage responses also initiate and direct T cells/adaptive immunity to provide additional protection such as Th1 (cytotoxic) or Th2 (antibody-mediated) type responses. ⋯ These findings indicate that the long held notion that adaptive immunity controls innate immunity was backward: a sea change in understanding how immune responses occur. The clinical impact of M1/kill and M2/repair responses is immense playing pivotal roles in curing (or causing) many diseases including infections, cancer, autoimmunity, and atherosclerosis. How M1/M2 came to be is an interesting story that, like life, involved Direction, Determination, Discouragement, and Discovery.
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Mast cells (MCs) are recognized to participate in the regulation of innate and adaptive immune responses. Owing to their strategic location at the host-environment interface, they control tissue homeostasis and are key cells for starting early host defense against intruders. ⋯ Furthermore, rather than only serving as effector cells, MCs are now recognized to induce T cell activation, recruitment, proliferation, and cytokine secretion in an antigen-dependent manner and to impact on regulatory T cells. This review synthesizes recent developments in MC-T cell interactions, discusses their biological and clinical relevance, and explores recent controversies in this field of MC research.
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Frontiers in immunology · Jan 2015
ReviewImmune Reactivation by Cell-Free Fetal DNA in Healthy Pregnancies Re-Purposed to Target Tumors: Novel Checkpoint Inhibition in Cancer Therapeutics.
The role of the immune system in cancer progression has become increasingly evident over the past decade. Chronic inflammation in the promotion of tumorigenesis is well established, and cancer-associated tolerance/immune evasion has long been appreciated. Recent developments of immunotherapies targeting cancer-associated inflammation and immune tolerance, such as cancer vaccines, cell therapies, neutralizing antibodies, and immune checkpoint inhibitors, have shown promising clinical results. ⋯ One such approach is comparing trophoblastic growth and regulation to tumor invasion and immune escape. Novel concepts regarding immune activation in pregnancy, especially reactivation of the immune system at labor through toll like receptor engagement by fetal derived DNA, may be applicable to cancer immunotherapy. This review summarizes mechanisms of inflammation in cancer, current immunotherapies used in the clinic, and suggestions for looking beyond oncology for novel methods to reverse cancer-associated tolerance and immunologic exhaustion utilizing mechanisms encountered in normal human pregnancy.
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Frontiers in immunology · Jan 2015
ReviewModulating the Innate Immune Response to Influenza A Virus: Potential Therapeutic Use of Anti-Inflammatory Drugs.
Infection by influenza A viruses (IAV) is frequently characterized by robust inflammation that is usually more pronounced in the case of avian influenza. It is becoming clearer that the morbidity and pathogenesis caused by IAV are consequences of this inflammatory response, with several components of the innate immune system acting as the main players. It has been postulated that using a therapeutic approach to limit the innate immune response in combination with antiviral drugs has the potential to diminish symptoms and tissue damage caused by IAV infection. ⋯ However, the dissection of those pathways is very complex given the numerous components regulated by the same factors (i.e., NF kappa B transcription factors) and the large number of players involved in this regulation, some of which may be undescribed or unknown. This article provides a comprehensive review of the current knowledge regarding the innate immune responses associated with tissue damage by IAV infection, the understanding of which is essential for the development of effective immunomodulatory drugs. Furthermore, we summarize the recent advances on the development and evaluation of such drugs as well as the lessons learned from those studies.
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Frontiers in immunology · Jan 2015
ReviewRecognition of Microbial Glycolipids by Natural Killer T Cells.
T cells can recognize microbial antigens when presented by dedicated antigen-presenting molecules. While peptides are presented by classical members of the major histocompatibility complex (MHC) family (MHC I and II), lipids, glycolipids, and lipopeptides can be presented by the non-classical MHC member, CD1. The best studied subset of lipid-reactive T cells are type I natural killer T (iNKT) cells that recognize a variety of different antigens when presented by the non-classical MHCI homolog CD1d. iNKT cells have been shown to be important for the protection against various microbial pathogens, including B. burgdorferi, the causative agents of Lyme disease, and S. pneumoniae, which causes pneumococcal meningitis and community-acquired pneumonia. ⋯ The subsequent cytokine response in turn lower the threshold of TCR-mediated iNKT cell activation, especially when weak microbial or even self-antigens are presented during the cause of the infection. In summary, iNKT cells can be directly activated through TCR triggering of strong antigens, while cytokines produced by the innate immune response may be necessary for TCR triggering and iNKT cell activation in the presence of weak antigens. Here, we will review the molecular basis of iNKT cell recognition of glycolipids, with an emphasis on microbial glycolipids.