Rickettsia conorii, but not R. montanensis, may be able to restore host cell homeostasis by increasing ER folding capacity. (A,B) Prediction model of alterations in proteasome and protein processing in endoplasmic reticulum activity, based on changes in the abundance of host proteins, that are induced by the infection of THP-1 macrophages with R. conorii
(A) or R. montanensis
(B). Increase/decrease in the abundance of host enzymes are predicted to contribute with increase/decrease in activity and are represented in red and blue, respectively. Increase, no alteration, or decrease in the abundance of host enzymes are predicted to contribute with increase, unchanged or decrease activity for the respective biological function and are represented in red, black, and blue arrows, respectively. (A) In R. conorii-infected THP-1 macrophages, several proteasome and immunoproteasome activator subunits are underrepresented at 24 h post-infection, which may lead to a decrease in antigen peptide generation, and subsequent decrease in antigen presentation by MHC complex Type I, and bacterial evasion from immune system surveillance. Decrease in proteasome activity may lead to an accumulation of misfolded proteins in ER, inducing ER stress. However, R. conorii specifically increases the abundance of several ER proteins involved protein translocation, folding, and quality control, which may be a compensatory mechanism activated by the UPR. (B) In R. montanensis-infected THP-1 macrophages, several proteasome and immunoproteasome activator subunits are also underrepresented at 24 h post-infection, which may lead to a decrease in antigen peptide generation (ii), and subsequent antigen presentation by MHC class I and bacteria evasion from immune system surveillance. Decrease in proteasome activity may lead to an accumulation of misfolded proteins and induction of ER stress. However, in contrast with R. conorii, R. montanensis infection did not result in increased levels of ER quality control components, likely resulting in the inability of R. montanensis to restore host cell homeostasis (see Table 5 for details).