Signalling from Toll-like receptors (TLRs) initiates the innate immune response, the body’s first line of defence against invading microbes. Because the adaptor molecule myeloid differentiation factor 88 (MYD88) is required for TLR signalling, MYD88 deficiency causes a human primary immunodeficiency syndrome. Here, van der Vaart et al. characterise a zebrafish line that expresses truncated Myd88. Zebrafish myd88 mutants, they report, are more susceptible to infection by bacterial pathogens than are wild-type fish. Moreover, expression of many (but not all) of the transcription factors, signalling factors and effector molecules that are central to innate immunity is dependent on Myd88 signalling during bacterial infections. These and other results establish the zebrafish myd88 mutant as a valuable tool for studying the role of TLR signalling in innate immune processes underlying infectious disease and disorders associated with immune dysregulation, such as cancer. Page 841

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