Fever Alters Immune Cells So They Can Better Reach Infections

Summary: Researchers shed light on how a fever helps our immune systems fight infection. The study reports high temperature alters surface proteins of lymphocytes, making it easier for them to travel through blood vessels to reach infection sites.

Source: Cell Press.

Fever is known to help power up our immune cells, and scientists in Shanghai have new evidence explaining how. They found in mice that fever alters surface proteins on immune cells like lymphocytes to make them better able to travel via blood vessels to reach the site of infection. Their work appears on January 15 in the journal Immunity.

“One good thing about fever is that it can promote lymphocyte trafficking to the site of infection, so you will have more immune cells in the infected region that will get rid of the pathogen,” says Shanghai Institute of Biochemistry and Cell Biology (SIBCB) Professor and senior author JianFeng Chen.

To get to an infection, white blood cells need to adhere to the blood vessel and then transmigrate into the infected tissue or lymph node. During this step, molecules known as integrins are expressed on the surface of lymphocytes. Integrins are cell adhesion molecules that control lymphocyte trafficking during inflammation.

Chen and colleagues discovered that fever increases the expression of heat shock protein 90 (Hsp 90) in T lymphocytes. This protein binds to a type of integrin on the lymphocytes — α4 integrins — which promote lymphocyte adhesion to the blood vessel and ultimately to expedited migration to the site of infection.

The researchers learned that fever-induced Hsp90 binds to the integrin tail and induces integrin activation. Moreover, one Hsp90 can bind to two integrins leading to a clustering of integrins on the lymphocyte surface. As a result, the clustered integrins activate a signaling pathway that promotes lymphocyte transmigration.

“Our findings show that this mechanism not only applies to lymphocytes but also to innate immune cells like monocytes,” says Chen. “It is a general mechanism that can apply to lots of different immune cells expressing α4 integrins.”

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The researchers learned that fever-induced Hsp90 binds to the integrin tail and induces integrin activation. NeuroscienceNews.com image is in the public domain.

The team also used animal studies of bacterial infection and other fever models to confirm their findings. When the pathway between the Hsp90 and integrin was blocked, study mice died quickly. They also learned that this mechanism is very temperature-specific. “In this paper, we found the Hsp90 can only be induced at a temperature above 38.5°C,” says Chen, explaining how the mechanism is targeted and effective, yet reversible.

The researchers also believe other stresses, not just fever, can induce Hsp90 expression. “That’s why we think that in different situations, such as autoimmune disease and cancer, this Hsp90-α4 integrin pathway may be involved,” says Chen. In autoimmune disease, aberrant trafficking of immune cells to different organs or tissues may lead to disease. “But if you block this pathway, you can maybe inhibit the trafficking of the immune cells during chronic inflammation or in autoimmune diseases,” he says.

About this neuroscience research article

Source: Cell Press
Publisher: Organized by NeuroscienceNews.com.
Image Source: NeuroscienceNews.com image is in the public domain.
Original Research: Open access research for “Fever Promotes T Lymphocyte Trafficking via a Thermal Sensory Pathway Involving Heat Shock Protein 90 and α4 Integrins” by ChangDong Lin et al in Immunity. Published January 16 2019.
doi:10.1016/j.immuni.2018.11.013

Cite This NeuroscienceNews.com Article
Cell Press”Fever Alters Immune Cells So They Can Better Reach Infections.” NeuroscienceNews. NeuroscienceNews, 16 January 2019.
<http://neurosciencenews.com/fever-immune-cells-10563/>.
Cell Press(2019, January 16). Fever Alters Immune Cells So They Can Better Reach Infections. NeuroscienceNews. Retrieved January 16, 2019 from http://neurosciencenews.com/fever-immune-cells-10563/
Cell Press”Fever Alters Immune Cells So They Can Better Reach Infections.” http://neurosciencenews.com/fever-immune-cells-10563/ (accessed January 16, 2019).

Abstract

Fever Promotes T Lymphocyte Trafficking via a Thermal Sensory Pathway Involving Heat Shock Protein 90 and α4 Integrins

Fever is an evolutionarily conserved response that confers survival benefits during infection. However, the underlying mechanism remains obscure. Here, we report that fever promoted T lymphocyte trafficking through heat shock protein 90 (Hsp90)-induced α4 integrin activation and signaling in T cells. By inducing selective binding of Hsp90 to α4 integrins, but not β2 integrins, fever increased α4-integrin-mediated T cell adhesion and transmigration. Mechanistically, Hsp90 bound to the α4 tail and activated α4 integrins via inside-out signaling. Moreover, the N and C termini of one Hsp90 molecule simultaneously bound to two α4 tails, leading to dimerization and clustering of α4 integrins on the cell membrane and subsequent activation of the FAK-RhoA pathway. Abolishment of Hsp90-α4 interaction inhibited fever-induced T cell trafficking to draining lymph nodes and impaired the clearance of bacterial infection. Our findings identify the Hsp90-α4-integrin axis as a thermal sensory pathway that promotes T lymphocyte trafficking and enhances immune surveillance during infection.

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