Editors' ChoiceImmunology

Human Immunity—Naturally

Science Signaling  05 Aug 2008:
Vol. 1, Issue 31, pp. ec281
DOI: 10.1126/scisignal.131ec281

Animal models continue to influence our understanding of immunity to infection, but how accurately do they predict how our own immune systems respond to different pathogens? Von Bernuth et al. continue a series of studies in which they use rare human immune deficiencies to help unpick the roles played by distinct innate immune pathways. The study focuses on MyD88, a signaling adaptor that is crucial in mice for protection against a wide range of pathogens by connecting key Toll-like receptor (TLR) and interleukin-1 (IL-1) pathways to the activation of immune response genes. In contrast to findings in mice, deficiency of the same protein in the human patients caused susceptibility to only a handful of pyogenic bacteria, despite leaving the subjects with broad deficits in their TLR and IL-1 responses.

H. von Bernuth, C. Picard, Z. Jin, R. Pankla, H. Xiao, C.-L. Ku, M. Chrabieh, I. B. Mustapha, P. Ghandil, Y. Camcioglu, J. Vasconcelos, N. Sirvent, M. Guedes, A. B. Vitor, M. J. Herrero-Mata, J. I. Aróstegui, C. Rodrigo, L. Alsina, E. Ruiz-Ortiz, M. Juan, C. Fortuny, J. Yagüe, J. Antón, M. Pascal, H.-H. Chang, L. Janniere, Y. Rose, B.-Z. Garty, H. Chapel, A. Issekutz, L. Maródi, C. Rodriguez-Gallego, J. Banchereau, L. Abel, X. Li, D. Chaussabel, A. Puel, J.-L. Casanova, Pyogenic bacterial infections in humans with MyD88 deficiency. Science 321, 691-696 (2008). [Abstract] [Full Text]