Well, a PHOBIA could be considered a mental disorder. Does he really have a phobia, or is he borderline? The impact to his life is possibly more than just having clean surfaces in his house. How much time does he spend dealing with cleaning? Does it affect his ability to socialize? Does it affect his ability to perform a job by which he can support himself? etc.?
As to your question about infections and such, that is known as the hygiene hypothesis (WP). However, that is mostly associated with childhood immunities and allergies as opposed to the effects on adults.
“The natural immune system does not have as much to do as it did 50 years ago because we’ve increased our efforts to protect our children from dirt and germs,” says McMorris.
“Allergies are on the rise because our society has changed the way we live. As a result, people with allergies are having children with others who have allergies, which in turn creates a natural increase in the prevalence of allergies in our society.
The bottom line on this hypothesis is that more research is required.
He (Richard G. Barbers, M.D., USC professor of medicine at the Keck School) also gives credence to the hygiene hypothesis in that "we may be over-protecting kids, and their immune systems, consequently, do not become well-developed."
Barbers notes that only time and a lot more research will tell whether the hygiene hypothesis is valid, and whether, once again, parents should let their kids play in the dirt.
There is some indication though that cleaning too much may impact your well being, not in the way you posited in your question, but rather through reactions to all the cleaning agents.
“Some people scrub their toilet bowl with a product that contains ammonia to remove rust stains, then follow up by pouring down a shot of bleach. They think that extra little bit of effort will kill germs. Actually, they’re making chlorine gas, a caustic mixture that actually was used as a weapon during World War I,” Duberg says.
It is generally understood that interaction with beneficial germs is good for you. However, normal cleaning will not destroy these germs since they reside within you (unless his germaphobia induces him to take antibiotics). The human immune response doesn't particularly work that way.
The investigators show that "good" bacteria in the gut keep the immune system primed to more effectively fight infection from invading pathogenic bacteria. Altering the intricate dynamic between resident and foreign bacteria - via antibiotics, for example -- compromises an animal's immune response, specifically, the function of white blood cells called neutrophils.
Another component of your question relates to perhaps "boosting" your immune system. A reporting group known as the Vaccine Times reported on this with some interesting links and thoughts that may be of use (but would not support the idea that your friend is weakening himself to disease).
The immune system is a network of cells, tissues, and organs that work together to defend the body against attacks by “foreign” invaders. These are primarily microbes—tiny organisms such as bacteria, parasites, and fungi that can cause infections. Viruses also cause infections, but are too primitive to be classified as living organisms. The human body provides an ideal environment for many microbes. It is the immune system’s job to keep them out or, failing that, to seek out and destroy them.
Now, if your friend has suffered from germaphobia since a young age, if the hygiene hypothesis has any merit, I would wonder what his allergy status is.