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Escalation of Germinal Center Responses in Chronic Litomosoides sigmodontis Filarial Infection
Teresa Steffen1, Jesuthas Ajendra2, Marianne Koschel2
1Medical Clinic III for Oncology, Hematology, Immuno-Oncology and Rheumatology, University Hospital Bonn, University of Bonn, Bonn, Germany.
T follicular helper (TFH) cells are the primary CD4+ T helper cell subset providing help to B cells for efficient antibody responses in vaccination, allergy, autoimmunity, and infectious diseases. Despite their critical involvement in immunity, TFH cells' specific role in filarial infections remains unclear. Using the rodent filarial model Litomosoides sigmodontis, we examined TFH and germinal center (GC) B cell responses in lung-draining mediastinal lymph nodes (medLNs) over a 110-day infection period in naive and infected wildtype (WT) BALB/c mice, as well as eosinophil-deficient dblGATA mice, using flow cytometry and ELISA. We observed robust and prolonged TFH and GC B cell responses in medLNs of infected BALB/c mice, along with enduring IgG1 antibody responses next to a persistent systemic humoral immune response. We further provide evidence of dysregulated TFH/T follicular regulatory (TFR) cell ratios in medLNs. Finally, elevated TFH cell frequencies in medLNs of dblGATA mice reaffirm the significant role of eosinophils during chronic infection. In conclusion, our findings provide novel insights into population changes of TFH and GC B cells during filarial infection.
T follicular helper (TFH) cells are the primary CD4+ T helper cell subset providing help to B cells for efficient antibody responses in vaccination, allergy, autoimmunity, and infectious diseases. Despite their critical involvement in immunity, TFH cells' specific role in filarial infections remains unclear. Using the rodent filarial model Litomosoides sigmodontis, we examined TFH and germinal center (GC) B cell responses in lung-draining mediastinal lymph nodes (medLNs) over a 110-day infection period in naive and infected wildtype (WT) BALB/c mice, as well as eosinophil-deficient dblGATA mice, using flow cytometry and ELISA. We observed robust and prolonged TFH and GC B cell responses in medLNs of infected BALB/c mice, along with enduring IgG1 antibody responses next to a persistent systemic humoral immune response. We further provide evidence of dysregulated TFH/T follicular regulatory (TFR) cell ratios in medLNs. Finally, elevated TFH cell frequencies in medLNs of dblGATA mice reaffirm the significant role of eosinophils during chronic infection. In conclusion, our findings provide novel insights into population changes of TFH and GC B cells during filarial infection.
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