Control of Persistent Salmonella Infection Relies on Constant Thymic Output Despite Increased Peripheral Antigen-Specific T Cell Immunity

Goggins, J. Alan; Kurtz, Jonathan R.; McLachlan, James B.

doi:10.3390/pathogens9080605

Cited by 5 publications

(3 citation statements)

References 58 publications

(84 reference statements)

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“…S. Typhimurium persistently infects Slc11a1 +/+ mice [ 4 , 152 , 153 ] and CD4 + and CD8 + T cells [ 85 ] and IFNγ [ 4 ] are important in final clearance and IL-17 is also thought to be important [ 153 ]. Persistent infection in the spleen is associated with elevated numbers of neutrophils, dendritic cells and macrophages but with no increase in T cells [ 153 , 154 ]. These authors showed that CD8alpha+ DC and Gr-1+ cells (neutrophils) increased in the red pulp.…”

Section: Is There Anything Characteristic To the Immune Response During Persistent Infections?mentioning

confidence: 99%

Revisiting Persistent Salmonella Infection and the Carrier State: What Do We Know?

Foster¹,

Tang

Berchieri

et al. 2021

Pathogens

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One characteristic of the few Salmonella enterica serovars that produce typhoid-like infections is that disease-free persistent infection can occur for months or years in a small number of individuals post-convalescence. The bacteria continue to be shed intermittently which is a key component of the epidemiology of these infections. Persistent chronic infection occurs despite high levels of circulating specific IgG. We have reviewed the information on the basis for persistence in S. Typhi, S. Dublin, S. Gallinarum, S. Pullorum, S. Abortusovis and also S. Typhimurium in mice as a model of persistence. Persistence appears to occur in macrophages in the spleen and liver with shedding either from the gall bladder and gut or the reproductive tract. The involvement of host genetic background in defining persistence is clear from studies with the mouse but less so with human and poultry infections. There is increasing evidence that the organisms (i) modulate the host response away from the typical Th1-type response normally associated with immune clearance of an acute infection to Th2-type or an anti-inflammatory response, and that (ii) the bacteria modulate transformation of macrophage from M1 to M2 type. The bacterial factors involved in this are not yet fully understood. There are early indications that it might be possible to remodulate the response back towards a Th1 response by using cytokine therapy.

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Section: Is There Anything Characteristic To the Immune Response During Persistent Infections?mentioning

confidence: 99%

Revisiting Persistent Salmonella Infection and the Carrier State: What Do We Know?

Foster¹,

Tang

Berchieri

et al. 2021

Pathogens

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“…We showed a high diversity of TREC and KREC levels in all groups. Patients with CAP had the increased levels of TRECs compared to controls, which probably reflects the protective production of the thymus as an early response to infection [ 34 ]. These data are consistent with the findings of Cuvelier et al, who showed the protective reactive thymus hyperplasia and increased TRECs as a proxy for thymic output in adult patients with COVID-19 [ 35 ].…”

Section: Discussionmentioning

confidence: 99%

Pneumonia and Related Conditions in Critically Ill Patients—Insights from Basic and Experimental Studies

Kashatnikova

Khadzhieva

Kolobkov

et al. 2022

IJMS

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Pneumonia is an acute infectious disease with high morbidity and mortality rates. Pneumonia’s development, severity and outcome depend on age, comorbidities and the host immune response. In this study, we combined theoretical and experimental investigations to characterize pneumonia and its comorbidities as well as to assess the host immune response measured by TREC/KREC levels in patients with pneumonia. The theoretical study was carried out using the Columbia Open Health Data (COHD) resource, which provides access to clinical concept prevalence and co-occurrence from electronic health records. The experimental study included TREC/KREC assays in young adults (18–40 years) with community-acquired (CAP) (n = 164) or nosocomial (NP) (n = 99) pneumonia and healthy controls (n = 170). Co-occurring rates between pneumonia, sepsis, acute respiratory distress syndrome (ARDS) and some other related conditions common in intensive care units were the top among 4170, 3382 and 963 comorbidities in pneumonia, sepsis and ARDS, respectively. CAP patients had higher TREC levels, while NP patients had lower TREC/KREC levels compared to controls. Low TREC and KREC levels were predictive for the development of NP, ARDS, sepsis and lethal outcome (AUCTREC in the range 0.71–0.82, AUCKREC in the range 0.67–0.74). TREC/KREC analysis can be considered as a potential prognostic test in patients with pneumonia.

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“…They also produced far more of the immunoregulatory cytokine IL-10 compared to lymphoid CD4 + T cells, which were more likely to produce IFN-g. In addition, lack of thymic output prior to persistent S. Typhimurium infection results in a loss of control over infection, despite the fact that Salmonella specific CD4 + T cells are elevated (Goggins et al, 2020). It will be important to explore whether the thymus contributes more T cells to the lymphoid compartment or the hepatobiliary tissue.…”

Section: Salmonella Typhimurium Microbial Pathogenesis and Immune Evasion Of The Hepatobiliary Systemmentioning

confidence: 99%

Salmonella Biofilm Formation, Chronic Infection, and Immunity Within the Intestine and Hepatobiliary Tract

Harrell

Hahn

D’Souza

et al. 2021

Front. Cell. Infect. Microbiol.

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Within the species of Salmonella enterica, there is significant diversity represented among the numerous subspecies and serovars. Collectively, these account for microbes with variable host ranges, from common plant and animal colonizers to extremely pathogenic and human-specific serovars. Despite these differences, many Salmonella species find commonality in the ability to form biofilms and the ability to cause acute, latent, or chronic disease. The exact outcome of infection depends on many factors such as the growth state of Salmonella, the environmental conditions encountered at the time of infection, as well as the infected host and immune response elicited. Here, we review the numerous biofilm lifestyles of Salmonella (on biotic and abiotic surfaces) and how the production of extracellular polymeric substances not only enhances long-term persistence outside the host but also is an essential function in chronic human infections. Furthermore, careful consideration is made for the events during initial infection that allow for gut transcytosis which, in conjunction with host immune functions, often determine the progression of disease. Both typhoidal and non-typhoidal salmonellae can cause chronic and/or secondary infections, thus the adaptive immune responses to both types of bacteria are discussed with particular attention to the differences between Salmonella Typhi, Salmonella Typhimurium, and invasive non-typhoidal Salmonella that can result in differential immune responses. Finally, while strides have been made in our understanding of immunity to Salmonella in the lymphoid organs, fewer definitive studies exist for intestinal and hepatobiliary immunity. By examining our current knowledge and what remains to be determined, we provide insight into new directions in the field of Salmonella immunity, particularly as it relates to chronic infection.

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Control of Persistent Salmonella Infection Relies on Constant Thymic Output Despite Increased Peripheral Antigen-Specific T Cell Immunity

Cited by 5 publications

References 58 publications

Revisiting Persistent Salmonella Infection and the Carrier State: What Do We Know?

Revisiting Persistent Salmonella Infection and the Carrier State: What Do We Know?

Pneumonia and Related Conditions in Critically Ill Patients—Insights from Basic and Experimental Studies

Salmonella Biofilm Formation, Chronic Infection, and Immunity Within the Intestine and Hepatobiliary Tract

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