Detection of Bacterial Antigens and Alzheimer\u27s Disease-like Pathology in the Central Nervous System of BALB/c Mice Following Intranasal Infection with a Laboratory Isolate of Chlamydia pneumoniae

Pathology consistent with that observed in Alzheimer’s disease (AD) has previously been documented following intranasal infection of normal wild-type mice with Chlamydia pneumoniae (Cpn) isolated from an AD brain (96-41). In the current study, BALB/c mice were intranasally infected with a laboratory strain of Cpn, AR-39, and brain and olfactory bulbs were obtained at 1-4 months post-infection (pi). Immunohistochemistry for amyloid beta or Cpn antigens was performed on sections from brains of infected or mock-infected mice. Chlamydia-specific immunolabeling was identified in olfactory bulb tissues and in cerebrum of AR-39 infected mice. The Cpn specific labeling was most prominent at 1 month pi and the greatest burden of amyloid deposition was noted at 2 months pi, whereas both decreased at 3 and 4 months. Viable Cpn was recovered from olfactory bulbs of 3 of 3 experimentally infected mice at 1 and 3 months pi, and in 2 of 3 mice at 4 months pi. In contrast, in cortical tissues of infected mice at 1 and 4 months pi no viable organism was obtained. At 3 months pi, only 1 of 3 mice had a measurable burden of viable Cpn from the cortical tissues. Mock-infected mice (0 of 3) had no detectable Cpn in either olfactory bulbs or cortical tissues. These data indicate that the AR-39 isolate of Cpn establishes a limited infection predominantly in the olfactory bulbs of BALB/c mice. Although infection with the laboratory strain of Cpn promotes deposition of amyloid beta, this appears to resolve following reduction of the Cpn antigen burden over time. Our data suggest that infection with the AR-39 laboratory isolate of Cpn results in a different course of amyloid beta deposition and ultimate resolution than that observed following infection with the human AD-brain Cpn isolate, 96-41. These data further support that there may be differences, possibly in virulence factors, between Cpn isolates in the generation of sustainable AD pathology

Assessment of the impact of race and proxies of socioeconomic status on the prevalence and health outcome of peripartum cardiomyopathy (PPCM) using the “All of Us” Databank

Background: Peripartum Cardiomyopathy (PPCM) is a form of cardiomyopathy occurring during the last month of pregnancy or within months after giving birth in women with previously normal hearts. PPCM is an idiopathic systolic dysfunction that causes a reduced left ventricle ejection fraction. The estimated incidence of PPCM worldwide is 1 diagnosis out of 2,000 live births, and the causes of PPCM remain unknown. A retrospective cohort study conducted at the University of Pennsylvania Health System by Getz et al. showed that black race and socioeconomic proxies (like neighborhood disadvantage index (NDI)) were independently associated with sustained cardiac dysfunction (Getz et al., Am Heart J 2021). This study also showed that from all the components of NDI (education, high rental occupied housing, annual income below poverty line, female headed household, adults unemployed, adults on public assistance), low education and high rental occupied housing were significantly associated with sustained cardiac dysfunction. The central aim of the present project is to assess the effect of socioeconomic proxies (including NDI, lack of access to health care and food insecurity) on the prevalence of sustained cardiac dysfunction from PPCM across the US using the “All of Us” databank. A secondary aim is to test the compliance of the All of Us database capacity to interrogate this potential association. Lastly, we aim to compare the results obtained from the All of Us database with the UK Biobank. Methods: The All of Us databank (Ramirez et al., Patterns 2022; The All of US Research Program, NEJM 2019) will be used to conduct a retrospective cohort study to assess how proxies of socioeconomic status may affect the incidence and prevalence of sustained cardiac dysfunction from PPCM across different ethnicities in the US. The All of Us database focuses on enrolling people in the US from diverse groups that have historically been underrepresented in medical research. Therefore, it includes a more diverse population than the population targeted in the retrospective study conducted at the University of Pennsylvania in which only black women from Philadelphia, PA, were included. To further interrogate the impact that geographic location and population ethnicity may have on the prevalence of sustained cardiac dysfunction from PPCM, the results obtained from the “All of Us” database will be compared against data obtained from the UK Biobank. Expected Results: We expect that the socioeconomic proxies interrogated in this study will have a significant impact on the prevalence of sustained cardiac dysfunction from PPCM. Current knowledge is limited on how socioeconomic status affects sustained cardiac dysfunction resulting from PPCM. Previous studies have been done on populations restricted to small geographic areas and did not analyze factors such as food security, access to care, or disability status. Understanding how these factors affect the incidence and prevalence of sustained cardiac dysfunction from PPCM may be used to improve prevention, early diagnosis, and management of PPCM

Differences in the immune response during the acute phase of E-55+ murine leukemia virus infection in progressor BALB and long term nonprogressor C57BL mice.

E-55+ murine leukemia virus infection of both progressor (BALB) and long term nonprogressor (C57BL) mouse strains is characterized by an acute and a persistent phase of infection. During the acute phase, progressor strains require CD8+ T cells to decrease virus burden, whereas the long term nonprogressor strains do not. In the present studies the immune response in BALB and C57BL mice during the acute phase of E-55+ murine leukemia virus infection was examined. The results demonstrate that BALB mice produce both IL-4 and IFN-gamma, in contrast to C57BL mice, which produce only IFN-gamma. In BALB mice, IL-4 production results in the absolute requirement for CD8+ T cells to reduce the virus burden during the acute phase of infection. The anti-virus immune response in these mice is IFN-gamma dependent. On the other hand, C57BL mice do not produce IL-4 and, in the absence of both CD8+ T cells and IFN-gamma, still generate an effective anti-virus immune response. Genetic studies suggest that these distinct immune responses are regulated by more than one non-MHC-linked gene. Two candidate regions that may encode this gene(s), located on chromosomes 7 and 19, respectively, were identified by recombinant inbred strain linkage analysis