West Nile virus (WNV) is a mosquito-borne flavivirus in the Japanese encephalitis antigenic group. It was first isolated in 1937 from a febrile woman in Omogo in the West Nile district of Uganda [ 1 x 1 Hubalek, Z and Halouzka, J. West Nile fever—a reemerging mosquito‐borne viral disease in Europe. Emerg Infect Dis. 1999; 5: 643–650 Crossref | PubMed | Google Scholar See all References 1 ]. WNV has a natural transmission cycle in Culex spp. mosquitoes and wild and captive birds [ 2 x 2 Rossi, SL, Ross, TM, and Evans, JD. West Nile virus. Clin Lab Med. 2010; 30: 47–65 Abstract | Full Text | Full Text PDF | PubMed | Scopus (80) | Google Scholar See all References 2 ]. In contrast, humans and horses are incidental dead-end hosts [ 3 x 3 Kramer, LD, Li, J, and Shi, PY. West Nile virus. Lancet Neurol. 2007; 6: 171–181 Abstract | Full Text | Full Text PDF | PubMed | Scopus (185) | Google Scholar See all References 3 ]. The enzootic/epizootic cycle is strictly linked to the period of activity of the arthropod vectors, which, in Europe, results in a season of WNV activity that, depending on the different latitude, ranges from mid-June to mid-November [ 4 x 4 Angelini, P, Tamba, M, Finarelli, AC et al. West Nile virus circulation in Emilia‐Romagna, Italy: the integrated surveillance system 2009. Euro Surveill. 2010; 15: 19547 PubMed | Google Scholar See all References , 5 x 5 Reiter, P. West Nile virus in Europe: understanding the present to gauge the future. Euro Surveill. 2010; 15: 19508 PubMed | Google Scholar See all References ]. Since its first recognition in Uganda, the virus has gradually dispersed, via migratory birds, out of Africa to the more southerly regions of Europe, Asia, and Australasia [ 2 x 2 Rossi, SL, Ross, TM, and Evans, JD. West Nile virus. Clin Lab Med. 2010; 30: 47–65 Abstract | Full Text | Full Text PDF | PubMed | Scopus (80) | Google Scholar See all References 2 ]. This review highlights some of the most relevant aspects of WNV human infections in Europe.

Human cytomegalovirus (CMV) is a ubiquitous DNA virus that causes severe disease in patients with immature or impaired immune systems. During active infection, CMV modulates host immunity, and CMV-infected patients often develop signs of immune dysfunction, such as immunosuppression and autoimmune phenomena. Furthermore, active viral infection has been observed in several autoimmune diseases, and case reports have linked primary CMV infection and the onset of autoimmune disorders. In addition, CMV infection promotes allograft rejection and graft-versus-host disease in solid organ and bone marrow transplant recipients, respectively, further implicating CMV in the genesis and maintenance of immunopathological phenomena. The mechanisms by which CMV could induce inhibition of host defense, inflammation, and autoimmunity are discussed, as is the treatment of virus-induced immunopathology with antivirals.

Plasmacytoid dendritic cells (PDCs), the main producers of type I IFN in response to viral infection, are essential in antiviral immunity. In this study, we assessed the effect of human CMV (HCMV) infection on PDC function and on downstream B and T cell responses in vitro. HCMV infection of human PDCs was nonpermissive, as immediate-early but not late viral Ags were detected. HCMV led to partial maturation of PDCs and up-regulated MHC class II and CD83 molecules but not the costimulatory molecules CD80 and CD86. Regardless of viral replication, PDCs secreted cytokines after contact with HCMV, including IFN-α secretion that was blocked by inhibitory CpG, suggesting an engagement of the TLR7 and/or TLR9 pathways. In the presence of B cell receptor stimulation, soluble factors produced by HCMV-matured PDCs triggered B cell activation and proliferation. Through PDC stimulation, HCMV prompted B cell activation, but only induced Ab production in the presence of T cells or T cell secreted IL-2. Conversely, HCMV hampered the allostimulatory ability of PDCs, leading to decreased proliferation of CD4⁺ and CD8⁺ T cells. These findings reveal a novel mechanism by which HCMV differentially controls humoral and cell-mediate immune responses through effects on PDCs.

Pathogens transmitted to humans by phlebotomine sand flies are neglected, as they cause infectious diseases that are not on the priority list of national and international public health systems. However, the infections caused by protozoa of the Leishmania genus and viruses belonging to the Phlebovirus genus (family Phenuiviridae)—the most significant group of viruses transmitted by sand flies—have a relevant role for human pathology. These infections are emerging in the Mediterranean region and will likely spread in forthcoming decades, posing a complex threat to human health. Four species and 2 hybrid strains of Leishmania are pathogenic for humans in the Mediterranean Basin, with an estimated annual incidence of 239,500–393,600 cases of cutaneous leishmaniasis and 1,200–2,000 cases of visceral leishmaniasis. Among the phleboviruses, Toscana virus can cause neuroinvasive infections, while other phleboviruses are responsible for a typical “3-day fever”; the actual incidence of Phlebovirus infections in the Mediterranean area is unknown, although at least 250 million people are exposed. Here, we reviewed the current literature on epidemiology of sand fly–borne infections in the Mediterranean Basin, with a focus on humans. Our analysis indicates the need for increased public health activities directed to determine the disease burden of these infections as well as to improve their surveillance. Among the emerging challenges concerning sand fly–borne pathogens, the relationships between sand fly–borne protozoa and viruses should be considered in future studies, including epidemiological links between Leishmania and phleboviruses as well as the conditional capacity for these pathogens to be involved in interactions that may evolve towards increased virulence.

Macrophages (Mϕ) are first targets during human cytomegalovirus (HCMV) infection and are thought to be crucial for viral persistence and dissemination. However, since Mϕ are also a first line of defense and key modulators of the immune response, these cells are at the crossroad between protection and viral pathogenesis. To date, the Mϕ-specific contribution to the immune response against HCMV is still poorly understood. In view of the opposite roles of M1 and M2 Mϕ during initiation and resolution of the immune response, we characterized the effects of HCMV infection on classically activated M1 Mϕ and alternatively activated M2 Mϕ. Although HCMV susceptibility was higher in M2 Mϕ, HCMV established a productive and persistent infection in both types of Mϕ. Upon HCMV encounter, both types of Mϕ acquired similar features of classical activation and secreted high levels of proinflammatory cytokines and chemokines. As a functional consequence, conditioned media obtained from HCMV-infected M1 and M2 Mϕ potently activated freshly isolated monocytes. Finally, compared to HCMV-infected monocyte-derived dendritic cells, infected M1 and M2 Mϕ were more efficient in stimulating proliferation of autologous T cells from HCMV-seropositive donors at early times (24 h) postinfection, while the Mϕ immunostimulatory properties were reduced, but not abrogated, at later times (72 h postinfection). In summary, our findings indicate that Mϕ preserve proper antigen presentation capacity upon HCMV infection while enhancing inflammation, thus suggesting that Mϕ play a role in the maintenance of the large HCMV-specific T-cell repertoire in seropositive individuals.