Macrophages

Lung interstitial macrophages alter dendritic cell functions to prevent airway allergy in mice Bedoret, D. et al. J. Clin. Invest. 119, 3723–3738 (2009)

Lung dendritic cells (DCs) activated by microbial lipopolysaccharide (LPS) can promote T helper 2-type immune responses, but most of us do not develop allergic asthma, even though we are constantly inhaling environmental LPS. In co-culture experiments, purified interstitial macrophages, but not alveolar macrophages, were shown to inhibit LPS-mediated activation of DCs. DCs cultured with interstitial macrophages expressed lower levels of co-stimulatory molecules and secreted less of the p40 subunit of interleukin-12 (IL-12) and IL-23. Interstitial macrophages exerted this immunosuppressive effect on DCs by producing IL-10. Ex vivo cultured interstitial macrophages spontaneously produced IL-10, and LPS exposure increased their secretion of this anti-inflammatory cytokine. When interstitial macrophages were depleted by antibodies, mice developed excessive airway inflammatory responses against an innocuous antigen delivered with LPS.

Dendritic cells

Preformed portals facilitate dendritic cell entry into afferent lymphatic vessels Pflicke, H. & Sixt, M. J. Exp. Med. 7 Dec 2009 (doi: 10.1084/jem.20091739)

Leukocytes extravasating from the blood interact with endothelial cells in a complex, multi-step process to penetrate the underlying basement membrane, but dendritic cells (DCs) have been shown to enter lymphatics independently of cell–matrix interactions. A new in situ live cell imaging approach used in this study showed that the basement membrane of initial lymphatics is discontinuous. Low expression levels of basement membrane molecules and a lack of pericytes may lead to the formation of gaps in initial lymphatics. Approaching DCs inserted protrusions and then pulled the rest of their cell body through the gap, causing momentary expansion of the lymphatic gaps. This process was purely physical and did not require proteases or integrins. The DCs then pushed aside the endothelial flap valves to gain full access to the draining lymphatic.

Tumour immunology

Melanoma-associated fibroblasts modulate NK cell phenotype and antitumor cytotoxicity Balsamo, M. et al. Proc. Natl Acad. Sci. USA 106, 20847–20852 (2009)

Little is known about the contribution of different stromal cell types to immune suppression in the tumour microenvironment. To address this issue, the authors established primary fibroblast cell lines from melanoma metastases and cultured these cells with natural killer (NK) cells from healthy donors. Interleukin-2 (IL-2)-induced upregulation of the NK cell activating receptors NKp30, NKp44 and DNAM1 was suppressed in the presence of tumour-derived fibroblasts. In addition, their cytolytic activity was impaired. Using a transwell system and specific blocking antibodies, the authors found that cell–cell contact was required for inhibiting DNAM1 expression, whereas secretion of prostaglandin E2 (PGE2) by the tumour-derived fibroblasts (which is greatly increased in the presence of NK cells) mediated the inhibition of NKp30 and NKp44 upregulation.