As usual, jurisdiction matters. Some states have laws that would make the usual home defense against an invader a slam dunk for the defense. I'm not sure how the kind of gun I'd use would ever be an issue in MO with our castle doctrine law. In states without such protections, it may depend on your local prosecutor's office and police department- if the attitudes are very anti-RKBA, they may be inclined to be prejudiced against certain firearm types and that could make them more likely to file charges (but if they're of that bent, even using a 16 gauge side by side over a SBR'd and suppressed AR-15 wouldn't redeem you in their eyes).
If push came to shove, I'd have little worry about using a suppressed firearm in self defense in my home. I can see how others in some other states might be more resistant to doing that.