Hi Nick,
This is a very broad question to answer. I will try.
if your organization settings allow tracking of all emails that are reply to CRM EMail, you will be able to do this using a plugin or a custom workflow step.
If you decide to do a plugin, add code to Execute on create of an email activity. If the email address subject include "Deny", update the regarding object of the email (contact record) and set donosendmm to true.
depending on your org settings, your solution may be different. Please let me know if you need any clarification.
Regards,
Jithesh