Basophils: The neglected minority gains a new respect as antigen presenting cells

To function as an antigen-presenting cell, the cell must fulfill a number of criteria. Upon antigen exposure, the candidate cell must express MHC class II and co-stimulatory molecules. It must be able to take up and process antigen and localize to draining lymph nodes, where efficient T cell–antigen-presenting cell interactions take place. Ideally, the candidate cell would also express the relevant cytokines required for T cell differentiation, although other accessory cells may provide the required cytokines. Finally, the candidate cell must be able to induce CD4⁺ T cell proliferation and differentiation in in vitro and in vivo assays.
Differentiation of naïve CD4⁺ T cells into Th2 cells requires three signals: T cell receptor triggering through peptide antigen recognition in the context of MHC class II molecule, amplification of T cell receptor signaling via co-stimulatory molecules and the presence of appropriate cytokine. For Th2 cell differentiation, however, dendritic cells are not the one-stop shop for all three required signals since dendritic cells do not produce IL-4, the cytokine necessary for Th2 cell differentiation. This observation implies that other antigen-presenting cells, in addition to dendritic cells, may contribute to Th2 cell differentiation.
The studies by Artis and colleagues (Perrigoue et al, Nat Immunol 2009), Medzhitov and colleagues (Sokol al, Nat Immunol 2009), and Nakanishi and colleagues (Yoshimoto al, Nat Immunol 2009), use three different models and elegantly demonstrate that basophils meet the criteria for antigen-presenting cells for Th2 cell differentiation.
Artis and colleagues studied the intestinal helminth parasite Trichuris muris. They showed that CD11c-restricted expression of MHC class II was not sufficient to generate a Th2 inflammatory response. Medzhitov and colleagues investigated the role of basophils in Th2 response to protease antigen papain and OVA. They demonstrated that MHC expression on basophils was sufficient to drive Th2 cell differentiation. Nakanishi and colleagues focused on the role of basophils in augmentation of Th2 responses by antigen–IgE immune complexes.
With basophils added to the list of cells capable of antigen presentation to naïve CD4⁺ T cells, the question arises as to what is the dominant antigen-presenting cell in Th2 inflammatory responses. Four approaches were used to highlight the dominant role of basophils.
First, the authors showed that basophil depletion through treatment with a monoclonal antibody to FceRI significantly diminished Th2 cell differentiation. The second approach used diphtheria toxin in CD11c-DTR mice and demonstrated that depletion of dendritic cells did not alter Th2 cell differentiation in response to OVA plus papain Th2 immunity to T. muris. The third approach demonstrated that CD11c-restricted expression of MHC class II was not sufficient to induce Th2 cell differentiation in response to OVA plus papain or to protect against infection with T. muris. In the fourth approach, mice were immunized in the ear with papain and the ear was either left intact or removed after two hours in order to remove the source of tissue resident dendritic cells. The authors observed Th2 cell differentiation, albeit at lower levels, in the draining lymph node, despite removal of skin resident dendritic cells.
The idea that the basophil is the dominant antigen-presenting cell for Th2 cell differentiation is certainly intriguing, but its validation requires further investigation.

What discriminates danger signals from pathogens with that of damage to tissues

The immune system protects against infection by pathogenic microorganisms, but it also recognizes when the body has been injured. Burns, radiation exposure, and bruises all involve the immune system when responding to damaged tissue. Which signaling pathways recognize tissue damage and keep the resulting inflammatory response from getting out of hand? Patten recognition receptors, which recognize pathogens or components of injured cells (danger), trigger activation of the innate immune system. Whether and how the host distinguishes between danger- versus pathogen-associated molecular patterns remains unresolved. In seminal paper in Science (Vol. 323. no. 5922, pp. 1722 - 1725, March 2009), Chen and colleagues demonstrated an unique mechanisms by which the body differentiates between self- and non-self signals during danger.
They that CD24-deficient mice exhibit increased susceptibility to danger- (DAMPs) but not pathogen-associated molecular patterns (PAMPs). CD24 associates with high mobility group box 1 (HMGB1), heat shock protein 70 (HSP70), and heat shock protein 90 (HSP90), negatively regulates their stimulatory activity, and inhibits nuclear factor-kappa B (NF-B) activation. This occurs at least in part through CD24 association with Siglec-10 in humans or Siglec-G in mice. Our results reveal that the CD24-Siglec-G pathway protects the host against a lethal response to pathological cell death and discriminates danger- versus pathogen-associated molecular patterns. Through association with and inhibition of the molecules that are released after tissue damage, CD24 and Siglec-G protected mice from an otherwise lethal inflammatory response.

After a long time

Sorry friends for not being active in the previous months. Unfortunately, my India visit and subsequent work load contributed to the lack of time for the blog.
I request the contributors to keep posting messages not only about the opportunities but also about science.