Normal Establishment of Virus-Specific Memory CD8 T Cell Pool following Primary Infection during Pregnancy

Constantin, Carolyn M.; Masopust, David; Gourley, Tania; Grayson, Jason M.; Strickland, Ora L.; Ahmed, Rafi; Bonney, Elizabeth A.

doi:10.4049/jimmunol.179.7.4383

Cited by 50 publications

(57 citation statements)

References 41 publications

(37 reference statements)

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“…This view is consistent with observations that pregnant women are not generally more susceptible to infection but rather are specifically susceptible to a select group of organisms that infect the maternal-fetal interface, including L. monocytogenes (59). This view is also consistent with observations that maternal vaccination is effective, if not enhanced, during gestation (60)(61)(62) and that CD8 ϩ T cell responses to viral antigens are not significantly diminished in pregnant versus nonpregnant mice (63). These considerations thus underscore the importance of further research into intrauterine mechanisms that promote or impede the colonization and growth of organisms that seed the maternal-fetal interface from the blood.…”

Section: Discussionsupporting

confidence: 80%

Limited Colonization Undermined by Inadequate Early Immune Responses Defines the Dynamics of Decidual Listeriosis

et al. 2017

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The bacterial pathogen Listeria monocytogenes causes foodborne systemic disease in pregnant women, which can lead to preterm labor, stillbirth, or severe neonatal disease. Colonization of the maternal decidua appears to be an initial step in the maternal component of the disease as well as bacterial transmission to the placenta and fetus. Host-pathogen interactions in the decidua during this early stage of infection remain poorly understood. Here, we assessed the dynamics of L. monocytogenes infection in primary human decidual organ cultures and in the murine decidua in vivo. A high inoculum was necessary to infect both human and mouse deciduas, and the data support the existence of a barrier to initial colonization of the murine decidua. If successful, however, colonization in both species was followed by significant bacterial expansion associated with an inability of the decidua to mount appropriate innate cellular immune responses. The innate immune deficits included the failure of bacterial foci to attract macrophages and NK cells, cell types known to be important for early defenses against L. monocytogenes in the spleen, as well as a decrease in the tissue density of inflammatory Ly6C hi monocytes in vivo. These results suggest that the infectivity of the decidua is not the result of an enhanced recruitment of L. monocytogenes to the gestational uterus but rather is due to compromised local innate cellular immune responses.KEYWORDS Listeria monocytogenes, decidua, placenta T he pregnant uterus is a dynamic organ that supports fetoplacental growth, with many trophic functions provided by the decidua, the specialized endometrial tissue that encases the conceptus (1). The decidua also provides a unique immunological environment that blocks the maternal immune system from recognizing the conceptus as a foreign tissue and rejecting it as if it were a solid-organ transplant (2). As a consequence, this environment would be expected to provide opportunities for pathogens to infect the maternal-fetal interface. Indeed, infection of the decidua is now considered to be a critical first step in the hematogenous transmission of a variety of pathogens from mother to fetus (3-7). One such organism is the facultative, intracellular, Gram-positive bacterium Listeria monocytogenes, a clinically relevant foodborne pathogen that can cause severe disease in pregnant women. Once L. monocytogenes reaches the placenta, there are increased risks of severe maternal disease and pregnancy complications, including preterm labor and devastating fetal/neonatal morbidity and mortality (8, 9).Because of its experimental tractability, L. monocytogenes is an excellent model

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Section: Discussionsupporting

confidence: 80%

Limited Colonization Undermined by Inadequate Early Immune Responses Defines the Dynamics of Decidual Listeriosis

et al. 2017

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“…Thus, although the expansion of the TER-119 þ population caused a reduction in the proportion of splenic lymphocytes, it did not directly suppress their proliferation or induce apoptosis. These data along with previous reports demonstrating that the total number [31] and the function of splenic lymphocytes are retained [32][33][34] suggest the immune system is not globally suppressed during pregnancy, as has been proposed by others [35][36][37][38].…”

Section: Discussionsupporting

confidence: 70%

Pregnancy Alters the Proliferation and Apoptosis of Mouse Splenic Erythroid Lineage Cells and Leukocytes1

Norton

Fortner

Bizargity

et al. 2009

Biology of Reproduction

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Pregnancy induces dynamic changes in the maternal environment that include reversible modifications in response to systemic mediators and local signals. The spleen can be used to determine the effects of pregnancy on multiple cellular populations, including those of the erythroid lineage and the immune system. Current evidence suggests that the transient increase in the size of the spleen during pregnancy is due to the expansion of erythroid precursors. However, it is unclear what factors contribute to this increase. Moreover, the additional erythroid cells may compete with neighboring leukocytes for growth factors or space, and this may in turn alter the function of these populations. Therefore, we assessed proliferation and apoptosis throughout gestation using in vivo bromodeoxyuridine incorporation and the TUNEL assay, respectively. Here, we show that erythroid-lineage TER-119(+) cells expanded significantly in midgestation because of enhanced proliferation and diminished apoptosis. This correlated with increased expression of the erythropoietin receptor (Epor) and decreased expression of the death receptor Fas, respectively. Leukocytes demonstrated population-specific responses. Natural killer cells proliferated in early pregnancy. Both lymphocytes and CD11B(+) cells underwent enhanced proliferation during midgestation. In contrast, neutrophils exhibited augmented proliferation throughout pregnancy. These subset-specific alterations in proliferation and death in the spleen suggest that complex regulation of population dynamics exists during pregnancy.

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Section: Reversible Binding To Trophoblasts Protects Hcmvmentioning

confidence: 96%

“…In a murine model, lymphocytic choriomeningitis virus can be effectively removed from the maternal system through an active virus-specific, CD8 T-cell response yet still remain present in the placenta [17]. This indicates that the lack of clearance from the murine placenta is not caused by the lack of a maternal immune response [17]. The increased and prolonged presence of HCMV within the placenta increases the probability of entry into the fetal compartment even when viral levels are low or undetectable in maternal blood or urine [20].…”

Section: Reversible Binding To Trophoblasts Protects Hcmvmentioning

confidence: 99%

“…They bind to chondroitin sulfate A, which is highly expressed in the placental syncytiotrophoblast (ST) layer, where they cause placental damage associated with low-birth-weight babies [15,16]. Furthermore, lymphocytic choriomeningitis virus, a single-stranded RNA virus, in the mouse is rapidly cleared from all tissues except for the placenta [17]. The above are striking examples of possible adverse consequences of the 12-m 2 surface area of placental trophoblast present in term pregnancies that has been characterized as an immuneprivileged site [18,19].…”

Section: Introductionmentioning

confidence: 99%

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Human Cytomegalovirus Is Protected from Inactivation by Reversible Binding to Villous Trophoblasts1

Davey

Eastman

Hansraj

et al. 2011

Biology of Reproduction

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Human cytomegalovirus (HCMV) is the leading cause of congenital disease in the developed world. Transmission of HCMV to the fetus can occur through the villous placenta. Previously, we have shown that although syncytiotrophoblast (ST) can be productively infected, it is more likely that HCMV reaches the fetus through breaks in the ST than through basal release of progeny virus from infected ST. Progeny virus released on the maternal side could interact back with the ST and accumulate. In pregnancy, the organ distribution of disease burden is dramatically shifted, with the placenta reported as a reservoir for some pathogens. Thus, we propose that the ST layer functions as a viral reservoir, where HCMV is harbored and ultimately protected from degradation. Using primary cytotrophoblasts differentiated into an ST culture in vitro and challenged with HCMV, we have defined reversible binding between the virus and trophoblasts that protects the virus from degradation. This is blocked by treatment with low pH and neutralizing intravenous immunoglobulin. This reversible binding likely is to heparan sulfate proteoglycans, because heparin treatment blocks it. Importantly, we show that bound and released virus maintained in culture for at least 48 h results from inoculum and not progeny virus. Thus, the placenta has the potential to accumulate a relatively high steady-state level of virus within the intervillous space resulting from localized binding and release at the ST. A better understanding of the molecular interactions between HCMV and ST will provide insights regarding interventions to prevent or minimize congenital transmission.

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Normal Establishment of Virus-Specific Memory CD8 T Cell Pool following Primary Infection during Pregnancy

Cited by 50 publications

References 41 publications

Limited Colonization Undermined by Inadequate Early Immune Responses Defines the Dynamics of Decidual Listeriosis

Limited Colonization Undermined by Inadequate Early Immune Responses Defines the Dynamics of Decidual Listeriosis

Pregnancy Alters the Proliferation and Apoptosis of Mouse Splenic Erythroid Lineage Cells and Leukocytes1

Human Cytomegalovirus Is Protected from Inactivation by Reversible Binding to Villous Trophoblasts1

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