Cellular Immunity and Active Human Cytomegalovirus Infection in Patients with Septic Shock

Müller, Lutz von; Klemm, Anke; Durmus, Nilgün; Weiß, Manfred; Suger-Wiedeck, Heide; Schneider, Marion; Hampl, Walter; Mertens, Thomas

doi:10.1086/522429

Cited by 70 publications

(62 citation statements)

References 28 publications

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“…Between these extremes there are other less well-understood possibilities where immune surveillance may be unable to prevent viral reactivation, but it still may be competent in inhibiting systemic uncontrolled infection. Indeed, recent reports showed that critically ill immunocompetent patients and patients with septic shock may undergo systemic, but self-limiting, reactivation of HCMV (5,6). Furthermore, immunosuppressed patients transplanted with solid organs are susceptible to a statistical increase in mortality, transplant rejection, accelerated vascular diseases, and injury from other pathogens (7) that can be prevented by specific anti-HCMV therapy (8,9).…”

mentioning

confidence: 99%

Intense Antiextracellular Adaptive Immune Response to Human Cytomegalovirus in Very Old Subjects with Impaired Health and Cognitive and Functional Status

Vescovini¹,

Biasini²,

Telera³

et al. 2010

The Journal of Immunology

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Human aging is characterized by expanded and altered adaptive immune responses to human CMV (HCMV). It is unclear whether this expansion has its origins in age-related homeostatic disturbances or viral reactivation, whether anti-CMV immune surveillance may still be effective, and what are the consequences of this expanded immune response for health and longevity. We conducted an observational cross-sectional study in groups of HCMV-seropositive subjects aged ≥65 y of variable health status to compare the intensity of Ab responses against HCMV with those against EBV and with CD4+ and CD8+ T cell proinflammatory effector responses directed to HCMV-derived pp65 and immediate-early protein 1 synthetic peptides. Ab responses to HCMV, but not to EBV, and anti-HCMV CD4+, but not CD8+, T cell responses were more intense in elderly subjects aged ≥85 y in poor health and were inversely correlated with markers of functional activity and cognitive function. Therefore, humoral and CD4+ T cell anti-HCMV responses were specifically intensified in advanced aging associated with comorbidity and cognitive and functional impairments. Such a distinctive pattern of adaptive immunity indicates that immune responses targeting the extracellular phase of HCMV are increased in these elderly subjects and could represent an indirect effect of localized and undetectable HCMV reactivation. This study demonstrates that the oldest subjects in poor health with physical and mental impairment express intense functional immune responses to extracellular HCMV and suggests that they may be at risk for direct pathogenic effects by HCMV reactivation as well as indirect pathogenic effects linked to proinflammatory anti-HCMV effector responses.

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mentioning

confidence: 99%

Intense Antiextracellular Adaptive Immune Response to Human Cytomegalovirus in Very Old Subjects with Impaired Health and Cognitive and Functional Status

Vescovini¹,

Biasini²,

Telera³

et al. 2010

The Journal of Immunology

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“…During the follow-up the frequency of Th1-cells signiWcantly increased in patients with septic shock following reactivation and recurrence [13]. The increase in CD4+ HCMV speciWc Th1-cells was presumably accompanied by increased activity of HCMV speciWc CD8+ cytotoxic Tcells as was shown before for patients after transplantation [39].…”

Section: => Direct Effects Of Disease (End-organ-disease)mentioning

confidence: 63%

“…We could show that HCMV recurrence was detected very similarly in groups with and without HCMV reactive Th1-cells, which means that CMV reactivation at the cellular level is not caused by immunosuppression. HCMV recurrence was followed by an increase of HCMV reactive Th1-cells which mostly failed to appear in the group without pp65-antigenemia [13] However, a subgroup of pp65-negative seropositive patients displayed a strong increase in HCMV reactive Th1-cells (Fig. 1) and we propose that reactivation without HCMV recurrence could have been the basis for stimulation and subsequent proliferation of HCMV reactive Th1-cells.…”

Section: Reactivationmentioning

confidence: 75%

“…Therefore, loss of NK-cell activity seems to be the result of NK-cell anergy and not of NK-cell depletion. This long-lasting NK-cell anergy could not be changed by testing puriWed NK-cells nor by addition of IL-2 in vitro [13,43]. The mechanism why NK-cells lost the ability to become activated is not clear but cytokines of SIRS could inhibit NK-cell activity in vitro, which was shown recently for IL-6 [44].…”

Section: => Direct Effects Of Disease (End-organ-disease)mentioning

confidence: 96%

“…Strict host restriction of HCMV and the lack of suitable cell culture models raise a number of questions which can be answered only in humans [12]. By analyzing antiviral immune functions of patients with septic shock we are now able for the Wrst time to evaluate the natural course of HCMV reactivation, recurrence, and viral clearance in a patient group without canonical immunosuppression [13].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Human cytomegalovirus infection and antiviral immunity in septic patients without canonical immunosuppression

Müller

Mertens

2008

Med Microbiol Immunol

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The human cytomegalovirus (HCMV) is a relevant pathogen in patients with immunosuppressive therapy; however, reactivation and subsequent recurrence occurs also in individuals without canonical immunosuppression as e.g., in patients with septic shock. Analyzing the impact of NK-and T-cell immunity on the natural course of HCMV infection in patients with septic shock, it became clear that the presence of HCMV reactive T-helper cells did not prevent the development of reactivation but, the control of active infection was achieved mostly by speciWc T-cells. NK-cells seemed to be dispensable for clearance of active infection in this patient group with long-lasting NK-cell anergy.

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Virological and immunological features of active cytomegalovirus infection in nonimmunosuppressed patients in a surgical and trauma intensive care unit

Chilet

Aguilar

Benet

et al. 2010

Journal of Medical Virology

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Cytomegalovirus (CMV) reactivation occurs frequently in critically ill patients. The natural course of CMV infection and the interaction between CMV and the adaptive immune system in this setting remain poorly defined. Fifty‐three CMV‐seropositive patients in a surgical and trauma intensive care unit were included in this study. The CMV DNA load in tracheal aspirates (TA) and plasma (PL) was monitored by qPCR. CMV‐specific T‐cell immunity was assessed by intracellular cytokine staining. Plasma TNF‐α levels were determined by ELISA. CMV reactivation occurred in 39.7% of patients (23% had CMV DNA detected only in TA). The analysis of TA allowed an earlier diagnosis in 28% of patients. Clearance of CMV DNAemia preceded that of CMV DNA in TA in some episodes. Peak CMV DNA levels were significantly higher in TA than in PL (P = 0.02). CMV reactivation developed in the presence of CMV‐specific T cells. Termination of CMV reactivation was associated with an expansion of functional CMV‐specific T cells. Plasma levels of TNF‐α did not allow for the prediction of the occurrence of CMV reactivation. CMV‐specific T‐cell immunity is preserved in most critically ill patients experiencing CMV reactivation. Analysis of respiratory specimens is imperative for an optimal monitoring of CMV reactivation in this setting. J. Med. Virol. 82:1384–1391, 2010. © 2010 Wiley‐Liss, Inc.

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Cellular Immunity and Active Human Cytomegalovirus Infection in Patients with Septic Shock

Abstract: A proinflammatory immune response may contribute to CMV reactivation in patients with septic shock. Adaptive T cell immunity, more likely than NK cell immunity, may contribute to termination of active CMV infection without antiviral therapy in these patients.

Cited by 70 publications

References 28 publications

Intense Antiextracellular Adaptive Immune Response to Human Cytomegalovirus in Very Old Subjects with Impaired Health and Cognitive and Functional Status

Intense Antiextracellular Adaptive Immune Response to Human Cytomegalovirus in Very Old Subjects with Impaired Health and Cognitive and Functional Status

Human cytomegalovirus infection and antiviral immunity in septic patients without canonical immunosuppression

Virological and immunological features of active cytomegalovirus infection in nonimmunosuppressed patients in a surgical and trauma intensive care unit

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