Subs, in answer to your question, setting your M22s to large will not damage them or your receiver. It simply allows the speakers to play their entire range of sound frequencies rather than starting to roll them off at the receivers crossover point (typically 80Hz).
The idea is to produce as wide a range of sound as smoothly as possible (e.g. no 'holes' in the sound frequencies from the absolute lowest to the absolute highest that your ear can hear).
However, given that you own M22s and a sub, i would recommend that you follow the advice to what JohnK and others had suggested (set M22s to small and use the subwoofer as you main speaker for bass).
For larger speakers, the towers, i have a different preference.
I've auditioned the M22s but i settled on buying the M60s instead. The full tower M60s (and of course the M80s and possibly some of the towers below the M60 as well), have a much greater bass extension than the M22s.
Hence, my M60s can play sound frequencies much lower than the M22s without such a large dropoff higher on the sound scale. Because the M60s have this capability, i've tested my preferences for bass by using the subwoofer for sound between 20Hz and 80Hz (approx.) and using the M60s for the sounds in this same range.
I did not like the sound of the subwoofer during music when it was allowed to play those frequencies right up to 80Hz. I preferred the tighter and less pronounced bass of the M60s as did my wife. But of course we still wanted to have some super rumbles during home theatre movie watching so the subwoofer still has its use.
If i have my M60s set to large, and they play sounds lower on the sound scale (e.g. lets say around 35 to 45Hz) before beginning to roll off (a function of their limitations), then THAT is where i would like to have the sub be used as a further extension of the M60s and to add some oomph in that extreme lower end.
So after some tweaking for sound in music primarily, i've now set my M60s to large and then used the crossover dial on the subwoofer to control how much or how little my M60s and subwoofer mix those low end sounds. At the present time my sub cross is set at about 50Hz with the gain (volume) at the 10 oclock mark and i find it integrates very nicely with the M60s.
Of course you can also try this with your M22s but when i played around with this configuration, i did not find that the M22s could produce sound frequencies quite low enough and well enough to make a difference whether i used the small or large settings but i did find their sound style to be very equivalent otherwise to the M60s.
"Those who preach the myths of audio are ignorant of truth. Research begets reality."