| First Author | Popescu M | Year | 2019 |
| Journal | J Immunol | Volume | 203 |
| Issue | 9 | Pages | 2415-2424 |
| PubMed ID | 31570507 | Mgi Jnum | J:280930 |
| Mgi Id | MGI:6370311 | Doi | 10.4049/jimmunol.1900484 |
| Citation | Popescu M, et al. (2019) TNF-alpha Contributes to Lymphoid Tissue Disorganization and Germinal Center B Cell Suppression during Intracellular Bacterial Infection. J Immunol 203(9):2415-2424 |
| abstractText | Bacterial, parasitic, and viral infections are well-known causes of lymphoid tissue disorganization, although the factors, both host and/or pathogen derived, that mediate these changes are largely unknown. Ehrlichia muris infection in mice causes a loss of germinal center (GC) B cells that is accompanied by the generation of extrafollicular T-bet(+) CD11c(+) plasmablasts and IgM memory B cells. We addressed a possible role for TNF-alpha in this process because this cytokine has been shown to regulate GC development. Ablation of TNF-alpha during infection resulted in an 8-fold expansion of GL7(+) CD38(lo) CD95(+) GC B cells, and a 2.5- and 5-fold expansion of CD138(+) plasmablasts and T-bet(+) memory cells, respectively. These changes were accompanied by a reduction in splenomegaly, more organized T and B cell zones, and an improved response to Ag challenge. CXCL13, the ligand for CXCR5, was detected at 6-fold higher levels following infection but was much reduced following TNF-alpha ablation, suggesting that CXCL13 dysregulation also contributes to loss of lymphoid tissue organization. T follicular helper cells, which also underwent expansion in infected TNF-alpha--deficient mice, may also have contributed to the expansion of T-bet(+) B cells, as the latter are known to require T cell help. Our findings contrast with previously described roles for TNF-alpha in GCs and reveal how host-pathogen interactions can induce profound changes in cytokine and chemokine production that can alter lymphoid tissue organization, GC B cell development, and extrafollicular T-bet(+) B cell generation. |
