Mucosal CCL28 Chemokine Improves Protection Against Genital Herpes Through Mobilization of Antiviral Effector Memory CCR10+CD44+ CD62L−CD8+ TEM cells and Memory CCR10+B220+CD27+ B Cells Into the Infected Vaginal Mucosa

• Published in: The Journal of immunology (1950) Vol. 211; no. 1; pp. 118 - 129
• Main Authors: Dhanushkodi, Nisha Rajeswari, Prakash, Swayam, Quadiri, Afshana, Zayou, Latifa, Srivastava, Ruchi, Tran, Jennifer, Dang, Vivian, Shaik, Amin Mohammed, Chilukurri, Amruth, Suzer, Berfin, De Vera, Phil, Sun, Miyo, Nguyen, Pauline, Lee, Ashley, Salem, Amirah, Loi, Joyce, Singer, Mahmoud, Nakayama, Takashi, Vahed, Hawa, Nesburn, Anthony B., BenMohamed, Lbachir
• Format: Journal Article
• Language: English
• Published: 01.07.2023
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.2300093

Four major mucosal-associated chemokines, CCL25, CCL28, CXCL14, and CXCL17 play an important role in protecting mucosal surfaces from infectious pathogens. However, their role in protection against genital herpes remains to be fully explored. The CCL28 is a chemoattractant for the CCR10 receptor-expressing immune cells and is produced homeostatically in the human vaginal mucosa (VM). In the present study, we investigated the CCL28/CCR10 chemokine axis’s role in mobilizing protective antiviral B- and T-cell subsets into the VM site of herpes infection. We report a significant increase in the frequencies of HSV-specific memory CCR10 + CD44 + CD8 + T cells, expressing high levels of CCR10, in herpes-infected asymptomatic (ASYMP) women compared to symptomatic (SYMP) women. Similarly, a significant increase in the CCL28 chemokine (a ligand of CCR10), was detected in the VM of herpes-infected ASYMP B6 mice, associated with the mobilization of high frequencies of HSV-specific effector memory CCR10 + CD44 + CD62L − CD8 + T EM cells and memory CCR10 + B220 + CD27 + B cells in the VM of HSV-infected asymptomatic mice. Inversely, compared to wild-type (WT) B6 mice, the CCL28 knockout (CCL28 (−/−) ) mice: ( i ) Appeared more susceptible to intravaginal infection and re-infection with HSV-2; ( ii ) Exhibited a significant decrease in the frequencies of HSV-specific effector memory CCR10 + CD44 + CD62L − CD8 + T EM cells and of memory CD27 + B220 + B cells in the infected VM. These findings suggest a critical role of the CCL28/CCR10 chemokine axis in the mobilization of anti-viral memory B and T cells within the VM to protect against genital herpes infection and disease.