Phosphoinositide 3-kinase (PI3K) activity is crucial for leukocyte function, but the roles of the four receptor-activated isoforms are unclear. Mice lacking heterotrimeric guanine nucleotide-binding protein (G protein)-coupled PI3Kgamma were viable and had fully differentiated neutrophils and macrophages. Chemoattractant-stimulated PI3Kgamma-/- neutrophils did not produce phosphatidylinositol 3,4,5-trisphosphate, did not activate protein kinase B, and displayed impaired respiratory burst and motility. Peritoneal PI3Kgamma-null macrophages showed a reduced migration toward a wide range of chemotactic stimuli and a severely defective accumulation in a septic peritonitis model. These results demonstrate that PI3Kgamma is a crucial signaling molecule required for macrophage accumulation in inflammation.

Pentraxins are a superfamily of conserved proteins that are characterized by a cyclic multimeric structure. The classical short pentraxins, C-reactive protein (CRP) and serum amyloid P component (SAP), are acute-phase proteins produced in the liver in response to inflammatory mediators. Short pentraxins regulate innate resistance to microbes and the scavenging of cellular debris and extracellular matrix components. In contrast, long pentraxins have an unrelated, long amino-terminal domain coupled to the carboxy-terminal pentraxin domain, and differ, with respect to short pentraxins, in their gene organization, chromosomal localization, cellular source, and in their stimuli-inducing and ligand-recognition ability. To investigate the in vivo function of the long pentraxin PTX3, we generated mice deficient in Ptx3 by homologous recombination. Ptx3-null mice were susceptible to invasive pulmonary aspergillosis. Ptx3 binds selected microbial agents, including conidia of Aspergillus fumigatus, and we found that susceptibility of Ptx3-null mice was associated with defective recognition of conidia by alveolar macrophages and dendritic cells, as well as inappropriate induction of an adaptive type 2 response. Thus, the long pentraxin Ptx3 is a secreted pattern-recognition receptor that has a non-redundant role in resistance to selected microbial agents, in particular to the opportunistic fungal pathogen Aspergillus fumigatus.

There is an urgent need to develop effective therapies for COVID-19. Here, we urge immunologists and clinicians to consider the potential of targeting the complement system in these patients.

During embryonic development, endothelial cells differentiate from a common precursor called angioblast and acquire organ-specific properties. One of the important determinants of endothelial cell differentiation is the local environment, and especially the interaction with surrounding cells. This interaction may occur through the release of soluble cytokines, cell-to-cell adhesion and communication, and the synthesis of matrix proteins on which the endothelium adheres and grows. The acquisition and maintenance of specialized properties by endothelial cells is important in the functional homeostasis of the different organs. For instance, in the brain, alteration of the blood-brain barrier properties may have important consequences on brain functional integrity. One of the major limitations to the study of endothelial cell heterogeneity is the fact that these cells are still difficult to isolate and culture from the microcirculation of different organs, and once in culture, they tend to lose their specialized properties. This finding suggests that we have to develop new culture systems, which possibly include coculture with other cell types. An important issue is to develop tools that can help in recognizing endothelial cells and their differentiated phenotype both in vivo and in tissue culture. In this review we give a short overview of the differentiated properties of the endothelium, considering a few examples of highly specialized endothelial cells, such as the brain or bone marrow microcirculation or high endothelial venules. We made a particular effort to list the most common markers of endothelial cell phenotypes. These molecules and related antibodies may be valuable tools for endothelial cell isolation and characterization.