The invention provides a method of treating a microbial infection in a subject and a method of improving an immune system response in a subject against a disease condition infection or virus thereof by administering an effective amount of a nucleoside short oligonucleotide compound or an analog thereof or a pharmaceutically acceptable salt racemate enantiomer diastereomer geometric isomer or tautomer thereof. In addition the invention provides methods for treating or preventing a viral infection bacterial infection parasitic infection or fungal infection in a subject (such as a human). The compounds of the invention include for example di and trinucleotide compounds as provided herein. The compounds of the invention are useful for different therapeutic applications including such as prophylactics and therapeutics. The invention also provides design and synthesis of a compound that is useful for various therapeutic applications as mentioned herein.