Macrophages allow entry of HIV in the urethra

Having suggested in 2011 that the urethra is a novel entry site for HIV, a team from the Institut Cochin (CNRS/Inserm/Université Paris Descartes, with the support of Anrs), has now confirmed this hypothesis and identified the cells and mechanisms brought into play: the immune system cells macrophages, present in the epithelium of the urethra, allow the entry of HIV. This work, published online on the website of the journal Mucosal Immunology, could make it possible to test novel HIV/AIDS prevention strategies.

While the mechanisms of rectal or vaginal infection in women are quite well described, penile infection in men remains poorly understood. Clinical studies conducted in the 2000s showed that circumcision could reduce the risk of infection in men by 60% during sexual intercourse. Following this work, the Institut Cochin team demonstrated that the mucous membrane on the inner layer of the foreskin was one of the main entry sites for HIV. However, since circumcision does not provide complete protection, it remained to be determined what other mucous sites in the penis could facilitate HIV infection.

To localize these entry sites, the researchers used penis tissue taken from healthy adult males during transgender surgery. HIV can, a priori, penetrate via three areas of the penis: the glans, the end of the urethra known as the fossa navicularis and the part of the urethra located inside the penis.. By placing the mucous membranes covering these three areas in contact with the HIV virus, the researchers observed that the glans and the fossa navicularis resist infection. On the other hand, the virus efficiently penetrates the penis through the urethra, which is also an entry site for many other sexually transmitted pathogens, such as gonococci or chlamydia (these results were presented in part at the international Conference on Retroviruses and Opportunistic Infections (CROI) in 2011).

The researchers are now focusing on molecular and cellular infection mechanisms. They have demonstrated that, in the urethra, the immune system cells responsible for the phagocytosis of pathogenic agents, known as macrophages, are the first to be invaded by HIV. This had never been observed in this type of mucous membrane. At the same time, the cells of the epithelium stop secreting the signals retaining the macrophages. Consequently, the infected macrophages leave the epithelium, allowing HIV to propagate. The researchers thus observed that, in the mucous membrane of the urethra, the TCD4+ lymphocytes - the main target of the virus - are not infected because they are immature. They could be infected later, after migration of HIV to the ganglia. The researchers now seek to determine whether the macrophages of the urethra constitute reservoirs preventing the virus from being completely eliminated by tritherapy treatment. This work is important from a fundamental viewpoint and it makes it possible to shed light on how the urethra can be an entry site for HIV in men, whether they are circumcised or not. It could also lead to the development of new prevention strategies.

Comments

  1. Joseph Lewis Joseph Lewis Japan says:

    Removal of all men's urethras?

    A few assumptions must be pointed out here, which are being sold as 100% fact.

    "Clinical studies conducted in the 2000s showed that circumcision could reduce the risk of infection in men by 60% during sexual intercourse."

    The clinical "studies" showed no such thing. Instead, the "researchers" took selected numbers from poorly conducted, early terminated, non-double-blinded trials and made a correlation, and attributed it to circumcision, *without any scientific explanation whatsoever.*

    Three hypotheses have been proposed since the introduction of the idea that circumcision can prevent HIV, all of them debunked. Dinh et al. demonstrated that there is no difference between the inner and outer foreskin. deWitte et al, demonstrated that, contrary to assumption, the Langerhans cells facilitated HIV transmission. Newer "research" has tried to attribute the facilitation of HIV transmission to infections caused by other pathogens in the preputial space. This last theory, however, would require "researchers" to prove that all of the non-circumcised men who acquired HIV did in fact suffer from said infections.

    The conductors of the said "trials" can't exactly pinpoint how the men, circumcised and non-circumcised alike, acquired HIV, assuming, without a scientific causal link, that their numbers (which are actually rather exaggerated, only a 1.3% absolute reduction) was actually caused by circumcision.

    This study seems to be another attempt to come up with a solid hypotheses, but commits the same error of assuming circumcision does anything a priori.

    So now are we to remove urethras in all men? What is the solution?

    Assuming it could actually be proven that circumcision prevents anything, why aren't researchers looking for a solution that does NOT involve the removal of the foreskin?

    This isn't research, this is quackery.

    Find a cure for AIDS. Not an alibi for genital mutilation.

    "Following this work, the Institut Cochin team demonstrated that the mucous membrane on the inner layer of the foreskin was one of the main entry sites for HIV."

    Where is this demonstration? Any reference? The Cochin team needs to help their colleagues in Rakai etc., because they are dying for a causal link. I'm actually very interested in seeing this demonstration.

    "However, since circumcision does not provide complete protection, it remained to be determined what other mucous sites in the penis could facilitate HIV infection."

    Bingo.

    And you can't eliminate these with surgery.

    What are you going to do now?

    "This work is important from a fundamental viewpoint and it makes it possible to shed light on how the urethra can be an entry site for HIV in men, whether they are circumcised or not. It could also lead to the development of new prevention strategies."

    I should hope so.

    This campaign to mutilate 20 million men in Africa is pure MADNESS.

  2. Frederick Rhodes Frederick Rhodes Mexico says:

    This mucosal entree point in the male prepuce has always been a maybe or maybe not, just speculation, never been obserbed before, not actually proven possibility, suggestion by proponents of infant circumcision. HIV is still thought to be aquired in the same manner as hepatitis C, through the blood. If you are going to suggest that our mucosal cells are in fact the entree point for HIV, then what about our sinuses, mouth and lungs? That would suggest HIV can be passed just like the Cold and Flu viruses, from a sneeze, hand shake, kissing grandma, as well as rough unprotected sex.

The opinions expressed here are the views of the writer and do not necessarily reflect the views and opinions of News Medical.
You might also like... ×
Study: Antiretroviral therapy fails to restore age-appropriate epigenetic patterns