In summary, we show that the ultimate adjuvant potential of CpG and CL097 may be determined by their differential induction of immunoregulatory factors like NO and PGE2. The synergistic enhancement of T cell expansion by dual inhibition of iNOS and COX-1/COX-2 in vitro may also reflect endogenous mechanisms that blunt T cell immunity to infectious diseases with chronic inflammation, such as TB [73], and might provide potential targets for host-directed therapies. Here, PTGS1 is linked to infectious disease.