B lymphocytes undergo TLR2-dependent apoptosis upon Shigella infection

Area of Science:

• Immunology
• Microbiology
• Cell Biology

Background:

• Antibody-mediated immunity to Shigella is short-lived, indicating impaired B cell responses.
• Shigella infection leads to B cell dysfunction, necessitating investigation into the underlying mechanisms.

Purpose of the Study:

• To investigate the interaction between Shigella and B lymphocytes.
• To elucidate the mechanisms by which Shigella induces B cell death and impairs immunity.

Main Methods:

• Ex vivo infection of human colonic tissue with S. flexneri.
• In vitro studies using human CL-01 B cell line and in vivo studies with mouse B lymphocytes.
• Analysis of type three secretion apparatus (T3SA)-dependent B cell death and IpaD protein interactions with TLR2.

Main Results:

• Shigella interacts with and invades B lymphocytes, inducing T3SA-dependent B cell death.
• The T3SA needle tip protein IpaD induces apoptosis in both invaded and non-invaded B cells via TLR2.
• Bacterial co-signals are necessary to sensitize B cells to IpaD-induced apoptosis and up-regulate TLR2 expression.
• Apoptotic B lymphocytes are found in rectal biopsies of infected individuals.

Conclusions:

• Shigella directly targets B lymphocytes, inducing apoptosis through the T3SA protein IpaD and TLR2 signaling.
• This direct targeting of B cells represents a novel mechanism employed by Shigella to evade host immune responses.
• The findings reveal a previously unrecognized pathway for immune evasion by Shigella, impacting adaptive immunity.