Pattern Recognition Receptors in Innate Immunity to Obligate Intracellular Bacteria

Abstract

Host pattern recognition receptors (PRRs) are crucial for sensing pathogenic microorganisms, initiating innate responses, and modulating pathogen-specific adaptive immunity during infection. Rickettsia spp., Orientia tsutsugamushi, Anaplasma spp., Ehrlichia spp., and Coxiella burnetii are obligate intracellular bacteria that can replicate only within host cells and must evade immune detection to successfully propagate. These five bacterial species are zoonotic pathogens of clinical or agricultural importance, yet uncovering how immune recognition occurs has remained challenging. Recent evidence from in vitro studies and animal models has yielded new insights into the types and kinetics of PRR activation during infection with Rickettsia spp., A. phagocytophilum, E. chaffeensis, and C. burnetii. However, much less was known about PRR activation in O. tsutsugamushi infection until the recent discovery of the role of the C-type lectin receptor Mincle during lethal infection in mice and in primary macrophage cultures. This review provides a brief summary of the clinical and epidemiologic features of these five bacterial infections, with a focus on the fundamental biologic facets of infection, and recent advances in host recognition. In addition, knowledge gaps regarding the innate recognition of these bacteria in the context of disease pathogenesis are discussed.

Protective effect of Schistosoma japonicum eggs on TNBS-induced colitis is associated with regulating Treg/Th17 balance and reprogramming glycolipid metabolism in mice

“…There is compelling evidence that the etiology of IBDs may be associated with various metabolic dysregulations ( Alexander et al., 2022 ; Zheng et al., 2022 ). It has been demonstrated that parasite-derived products have a strong ability to regulate metabolism in the host body ( Zhu et al., 2014 ; Cai et al., 2021 ; Fisher et al., 2021 ). Differentiation of T cells can be manipulated through modulating metabolic activity in vitro ( Chang et al., 2013 ).…”

Protective Immunity and Immunopathology in Ehrlichiosis

“…Inflammasomes are key components of the innate immune system and contribute to the initial host defense mechanism against pathogens. Inflammasomes recognize pathogen-derived molecules known as pathogen-associated molecular patterns (PAMPs) [69][70][71] as well as endogenous host-derived molecules, known as damage-associated molecular patterns (DAMPs), that are released from dying cells during stress or infection [72][73][74][75]. Inflammasomes are cytosolic multi-protein complexes that consist of intracellular nucleotide-oligomerization domain (NOD)-like receptor (NLR), nucleotide-binding domain, and leucine-rich repeat (LRR) containing proteins, or the absent in melanoma 2 (AIM2)-like receptors (ALRs), the adaptor protein apoptosis-associated speck-like protein containing a caspase activation and recruitment domain (ASC), and procaspases [76][77][78][79].…”

Orientia tsutsugamushi Infection Stimulates Syk-Dependent Responses and Innate Cytosolic Defenses in Macrophages

“…O. tsutsugamushi is a Gram-negative, lipopolysaccharide-negative coccobacillus, primarily infecting endothelial cells, monocytes, macrophages (MΦ), neutrophils, and dendritic cells [ 5 ]. Compared with other obligate intracellular bacteria such as Rickettsia , Ehrlichia , or Anaplasma , O. tsutsugamushi has unique yet poorly understood biology [ 6 ]. After the bacterium is internalized via endocytosis or phagocytosis, it rapidly (<4 h) escapes the endosome to freely inhabit the cytosol [ 5 ].…”