However, a remaining unresolved issue is why animals that lack CISH globally across all of these cell types demonstrate a type 2 bias.18 Humans with single nucleotide polymorphisms conferring reduced function of CISH show increased susceptibility to hepatitis B virus (HBV), bacteremia, tuberculosis (TB), and malaria53–55—observations consistent with our finding that CISH-deficient mice have increased susceptibility to Salmonella infection—but to our knowledge have not been reported to have allergic predilections. This evidence concerns the gene CISH and bacterial infectious disease with sepsis.