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Failure of CD4 T Cell-Deficient Hosts To Control Chronic Nontyphoidal Salmonella Infection Leads to Exacerbated Inflammation, Chronic Anemia, and Altered Myelopoiesis.

Abstract：

:Immunocompromised patients are more susceptible to recurrent nontyphoidal Salmonella (NTS) bacteremia. A key manifestation of HIV infection is the loss of CD4 T cells, which are crucial for immunity to Salmonella infection. We characterized the consequences of CD4 T cell depletion in mice where virulent Salmonella establish 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 in Salmonella-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 of Salmonella infection 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 to Salmonella infection.

journal_name

Infect Immun

journal_title

Infection and immunity

authors

Loomis WP,Delaney MA,Johnson ML,Cookson BT

doi

10.1128/IAI.00417-20

subject

Has Abstract

pub_date

2020-12-15 00:00:00

issue

eissn

0019-9567

issn

1098-5522

pii

IAI.00417-20

journal_volume

pub_type

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Failure of CD4 T Cell-Deficient Hosts To Control Chronic Nontyphoidal Salmonella Infection Leads to Exacerbated Inflammation, Chronic Anemia, and Altered Myelopoiesis.