💡 What if Our Mucous Membranes Held a Key to Slowing HIV?

In an article published in Mucosal Immunology, scientists show that IgA antibodies present in mucous membranes play a key role against HIV. By triggering the destruction of infected cells, which then allows the activation of killer lymphocytes, they enhance cooperation between innate immunity and adaptive immunity, paving the way for new strategies to limit the spread of the virus.

IgA Antibodies: A First Barrier Against Infections

Mucosal IgA antibodies represent the first line of defense of our body against infections that attack mucous membranes (like those of the nose, mouth, lungs, or genital tract).

Each antibody has a part called the Fab region, which varies from one antibody to another and allows for the recognition of specific antigens (foreign molecules present on the surface of viruses or bacteria).

IgA can also combat viruses thanks to another part common to all antibodies: the Fc domain. This domain allows for the destruction of infected cells via a mechanism called antibody-dependent cellular phagocytosis (or ADCP). This process is carried out by certain cells of the innate immune system, such as monocytes, which "eat" infected cells.

Previous studies have shown that injecting anti-HIV-1 IgG antibodies (a technique called passive immunization) could protect non-human primates. This protection depended on the action of CD8+ T lymphocytes, killer cells of the immune system, likely thanks to the ADCP performed by these IgG.

A Study Revealing the Key Role of IgA Against HIV

In a study published in the journal Mucosal Immunology, researchers compared the effects of phagocytosis of cells infected with HIV-1 when triggered by virus-specific antibodies, either in IgA or IgG form.

They discovered that phagocytosis mediated by IgA, present in mucous membranes, allowed for the destruction of infected cells but also for the presentation of viral antigens to CD8+ T lymphocytes and the activation of their cytotoxic function (their ability to kill infected cells). In contrast, IgG antibodies, more present in the blood, did not cause this effect.

Furthermore, after binding to IgA and triggering the phagocytosis of infected cells, monocytes reprogram into activated macrophages. These macrophages present a mixture of pro-inflammatory and anti-inflammatory properties and secrete pro-inflammatory chemokines (molecules that attract other immune cells).

IgA-mediated ADCP also makes monocytes more reactive to a new bacterial infection: they produce more cytokines like IL-6 and TNFα. This phenomenon is a sign of trained immunity, a recent form of memory of the innate immune system, which allows it to better react to future attacks.

All these observations show that there is a close link between adaptive (specific) immunity initiated by IgA and innate (natural) immunity.

This discovery paves the way for new strategies to prevent the spread of HIV, by exploiting the protective role of IgA antibodies and their ability to activate both the natural and specific defenses of our body.