Detection of bacterial antigens and Alzheimer’s disease-like pathology in the central nervous system of BALB/c mice following intranasal infection with a laboratory isolate of Chlamydia pneumoniae

Abstract

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.

A genetic signature including apolipoprotein Eε4 potentiates the risk of herpes simplex–associated Alzheimer's disease

“…These observations are consistent with the finding that amyloid b has antimicrobial activity [22][23][24]. There are other suggested AD-associated pathogens, among which cytomegalovirus (CMV) [25,26], human herpes virus 6 (HHV6) [27], and Chlamydophila pneumoniae (C. pneumoniae) [28,29] are highlighted here because they have the common ability to establish latent or chronic infections within the central nervous system (CNS).…”

HSV presence in brains of individuals without dementia: the TASTY brain series

“…Although this might in part be explained by the sensitivity of our analyses, recent studies are pointing towards the Aβ reaction being a part of the innate immune system (Itzhaki et al, 2016; Kumar et al, 2016), with a broad antimicrobial effect against bacteria, fungi and viruses including HSV (Bourgade et al, 2015; Soscia et al, 2010; White et al, 2014). Several bacteria and viruses have been demonstrated as being able to trigger the Aβ reaction in cultured cells and mice (Kristen et al, 2015; Little et al, 2014; Miklossy et al, 2006; Santana et al, 2012; Shipley et al, 2005). A possible explanation might therefore be that previous infections leave scars in the form of Aβ aggregations; however, certain persistent infections including HSV might continue to trigger the Aβ production for prolonged periods of time to produce accumulation of Aβ and ultimately Alzheimer's disease.…”

Rhamnolipids, Microbial Virulence Factors, in Alzheimer’s Disease

“…Moreover, it is alleged that the presence of bacterial antigens, derived from the bacterium Borrelia burgdorferi belonging in the spirochete phylum, in concomitance with genes in the brain of AD patients, demonstrate that these patients had undergone chronic Lyme neuroborreliosis [71]. Bacterial antigens and AD-like pathology have been detected in the CNS of BALB/c mice models resulting from intranasal infection due to a strain of Chlamydia pneumoniae [20]. An excessive amount of virulence markers encoded virulence-related genes which have been recorded to originate from Staphylococcus aureus strains isolated from hemodialysis catheters of Mexican patients; they were held responsible for nosocomial bacterial infections due to biofilm formation [72].…”

“…The continuous generation of bacterial components, considered as potent inflammatory agents, as well as their feedback from the pool of the dormant bacteria, may well justify the persistent, but mild-manifested inflammation, followed by inflammatory cytokine production, which is characteristic of many diseases [20]. Moreover, it is alleged that the presence of bacterial antigens, derived from the bacterium Borrelia burgdorferi belonging in the spirochete phylum, in concomitance with genes in the brain of AD patients, demonstrate that these patients had undergone chronic Lyme neuroborreliosis [71].…”

“…The surviving cells are able to expel strongly inflammatory components including LPSs [16]. The imputed role of pathogens in AD has been extensively reported for about over 200 different helical bacterial spirochete species [17], which may co-infect with other Gram-negative phylotypes [18][19][20][21][22][23][24][25][26][27][28][29].…”