One antibody for all and all antibodies for one: Antibodies against related flavi-viruses such as dengue (DENV) and West Nile (WNV) can cross-react with Zika virus (ZIKV) and could thereby increase disease severity. Bardina et al. tested whether DENV and WNV antibodies from humans, or even yellow fever vaccination, could enhance ZIKV infection. In a mouse model, low titers of DENV and WNV antibodies enhanced ZIKV viremia, especially in the spinal cord and testes, whereas high titers remained protective. Generally, WNV antibodies were less disease-enhancing than DENV antibodies, and, in macaques, yellow fever vaccination had very little effect. Science , this issue p. 175

Type 1 immunity gives fungi a foothold: Type 17 immune responses play a vital role against fungal infections of the mucosa. It remains unclear whether other types of immune responses can also contribute to host defense against these pathogens. The yeast Candida albicans prominently infects patients with autoimmune polyendocrinopathy–candidiasis–ectodermal dystrophy (APECED), an inherited disease caused by loss-of-function mutations in the AIRE gene. Break et al. report that the oral susceptibility of Aire -deficient mice to C. albicans is not due to aberrant type 17 responses. Rather, the overproduction of interferon-γ by local CD4 ⁺ and CD8 ⁺ T cells in these mice disrupts the epithelial barrier, which increases susceptibility to C. albicans invasion. Similar type 1 immune pathways are operational in APECED patients. Inhibition of interferon-γ or the JAK-STAT signaling pathway in mice ameliorates disease symptoms, suggesting potential future therapeutic interventions for certain classes of fungal disease. Science , this issue p. eaay5731

West Nile virus (WNV) is a re-emerging pathogen and the leading cause of epidemic encephalitis in the United States. Inflammatory monocytes are a critical component of the cellular infiltrate found in the CNS during WNV encephalitis, although the molecular cues involved in their migration are not fully understood. In mice, we previously showed that WNV infection induces a CCR2-dependent monocytosis that precedes monocyte migration into the CNS. Currently, the relative contribution of the CCR2 ligands, chemokines CCL2 and CCL7, in directing monocyte mobilization and leukocyte migration into the CNS is unclear. In this study, we demonstrate that, although both CCL2 and CCL7 are required for efficient monocytosis and monocyte accumulation in the CNS, only CCL7 deficiency resulted in increased viral burden in the brain and enhanced mortality. The enhanced susceptibility in the absence of CCL7 was associated with the delayed migration of neutrophils and CD8⁺ T cells into the CNS compared with WT or Ccl2^−/− mice. To determine whether CCL7 reconstitution could therapeutically alter the survival outcome of WNV infection, we administered exogenous CCL7 i.v. to WNV-infected Ccl7^−/− mice and observed a significant increase in monocytes and neutrophils, but not CD8⁺ T cells, within the CNS, as well as an enhancement in survival compared with Ccl7^−/− mice treated with a linear CCL7 control peptide. Our experiments suggest that CCL7 is an important protective signal involved in leukocyte trafficking during WNV infection, and it may have therapeutic potential for the treatment of acute viral infections of the CNS.