| First Author | Olayinka-Adefemi F | Year | 2021 |
| Journal | J Immunol | Volume | 207 |
| Issue | 5 | Pages | 1401-1410 |
| PubMed ID | 34380646 | Mgi Jnum | J:331196 |
| Mgi Id | MGI:6845016 | Doi | 10.4049/jimmunol.2100311 |
| Citation | Olayinka-Adefemi F, et al. (2021) Critical Roles of Phosphoinositide 3-Kinase delta in the Humoral Immune Response to Trypanosoma congolense Infection. J Immunol 207(5):1401-1410 |
| abstractText | PI3Kdelta is critical in generating humoral and regulatory immune responses. In this study, we determined the impact of PI3Kdelta in immunity to Trypanosoma congolense, an African trypanosome that can manipulate and evade Ab responses critical for protection. Upon infection with T. congolense, PI3Kdelta(D910A) mice lacking PI3Kdelta activity paradoxically show a transient enhancement in early control of parasitemia, associated with impaired production of regulatory IL-10 by B cells in the peritoneum. C57BL/6 wild-type (WT) mice treated with the PI3Kdelta inhibitor (PI3Kdeltai) Idelalisib showed a similar transient decrease in parasitemia associated with reduced IL-10. Strikingly, however, we find that PI3Kdelta(D910A) mice were ultimately unable to control this infection, resulting in uncontrolled parasitemia and death within 2 wk. Assessment of humoral responses revealed delayed B cell activation, impaired germinal center responses, and compromised Ab responses to differing degrees in PI3Kdelta(D910A) and PI3Kdeltai-treated mice. To test the role of Abs, we administered serum from WT mice to PI3Kdelta(D910A) mice and found that lethality was prevented by postinfection serum. Interestingly, serum from naive WT mice provided partial protection to PI3Kdelta(D910A) mutants, indicating an additional role for natural Abs. Together our findings suggest that although PI3Kdelta drives immune regulatory responses that antagonize early control of parasite growth in the peritoneum, it is also required for generation of Abs that are critical for protection from systemic trypanosome infection. The essential role of PI3Kdelta for host survival of African trypanosome infection contrasts with findings for other pathogens such as Leishmania, underlining the critical importance of PI3Kdelta-dependent humoral immunity in this disease. |
