Failure of CD4 T Cell-Deficient Hosts To Control Chronic Nontyphoidal Salmonella Infection Leads to Exacerbated Inflammation, Chronic Anemia, and Altered Myelopoiesis.
Failure of CD4 T Cell-Deficient Hosts To Control Chronic Nontyphoidal Salmonella Infection Leads to Exacerbated Inflammation, Chronic Anemia, and Altered Myelopoiesis.
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CD4 T 细胞缺陷宿主无法控制慢性非伤寒沙门氏菌感染，导致炎症加剧、慢性贫血和骨髓细胞生成改变。
DOI：
10.1128/iai.00417-20
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发表时间：
2020
影响因子：
3.1
通讯作者：
Cookson,BradT
中科院分区：
文献类型：
--
作者：
Loomis,WendyP;Delaney,MarthaA;Johnson,MatthewL;Cookson,BradT
Immunocompromised patients are more susceptible to recurrent nontyphoidalSalmonella(NTS) bacteremia. A key manifestation of HIV infection is the loss of CD4 T cells, which are crucial for immunity toSalmonellainfection. We characterized the consequences of CD4 T cell depletion in mice where virulentSalmonellaestablish chronic infection, similar to chronic NTS disease in humans.Salmonella-infected, CD4-depleted 129X1/SvJ mice remained chronically colonized for at least 5 weeks, displaying increased splenomegaly and more severe splenitis than infected mice with CD4 T cells. Mature erythrocytes, immature erythroid cells, and phagocytes accounted for the largest increase in splenic cellularity. Anemia, which is associated with increased mortality inSalmonella-infected humans, was exacerbated by CD4 depletion in infected mice and was accompanied by increased splenic sequestration of erythrocytes and fewer erythropoietic elements in the bone marrow, despite significantly elevated levels of circulating erythropoietin. Splenic sequestration of red blood cells, the appearance of circulating poikilocytes, and elevated proinflammatory cytokines suggest inflammation-induced damage to erythrocytes contributes to anemia and splenic retention of damaged cells in infected animals. Depleting CD4 T cells led to increased myeloid cells in peripheral blood, spleen, and bone marrow, as well as expansion of CD8 T cells, which has been observed in CD4-depleted humans. This work describes a mouse model ofSalmonellainfection that recapitulates several aspects of human disease and will allow us to investigate the interplay of innate and adaptive immune functions with chronic inflammation, anemia, and susceptibility toSalmonellainfection.
