# Virulent Rickettsia species utilize the CD300f phosphatidylserine-binding receptor on macrophages for host colonization and pathogenesis

> **NIH NIH R21** · UNIVERSITY OF MARYLAND BALTIMORE · 2022 · $231,750

## Abstract

PROJECT SUMMARY
 Rickettsia species are arthropod-borne obligate intracellular bacteria with both symbiotic and pathogenic
lifecycles. The global impact of rickettsial infections is highlighted by the resurgence of human infections with R.
rickettsii (etiologic agent of Rocky Mountain Spotted Fever) in Central and South America, reappearance of R.
conorii (etiologic agent of Boutonneuse Fever) in Europe, Middle East, and Africa9 and the recent outbreaks of
R. rickettsii and R. typhi (etiologic agent of murine typhus) in the USA. Unfortunately, our inadequate
understanding of Rickettsia-host interaction, in particular at the level on rickettsial engulfment via receptor-ligand-
mediated phagocytosis on professional host defense cells, like macrophages (MΦ), has significantly impaired
the development of effective therapeutics against these pathogens. To address these knowledge gaps, we
propose to: i) characterize the specific rickettsial outer membrane glycerophospholipid ligand(s) involved in the
phagocytic process of SFG and TG rickettsiae by MΦ, ii) decipher the role of efferocytic receptor, CD300f, in
facilitating host colonization of virulent Rickettsia species. Our preliminary work identified phosphatidylserine
(PS), a well-characterized “eat-me” signal involved in the phagocytosis of apoptotic cells (aka efferocytosis), as
a putative ligand on outer membrane of rickettsiae. We further validated PS as crucial ligand for engulfment of
R. typhi and R. rickettsii [Shelia Smith], two virulent bacteria representing the TG and SFG, respectively, by using
recombinant Annexin V, a molecule known to block PS-mediated efferocytosis, in bone marrow-derived
macrophages (BMMΦ). As PS-dependent phagocytosis requires PS-receptor recognition, we focused on
CD300f, a type I transmembrane cell surface receptors with a high binding affinity to PS. Using WT and CD300f-
/- BMMΦ, we showed that engulfment of R. typhi and R. rickettsii was dependent on CD300f expression, which
was further confirmed by αCD300f antibody-mediated neutralization assays on WT BMMΦ. We tested the role
of CD300f in vivo, by establishing mouse models of rickettsiosis with ~LD50 for both R. typhi and R. rickettsii
species in C57BL/6J WT mice and showed that, unlike WT mice, CD300f-/- animals were protected against
Rickettsia-induced lethality. Furthermore, in vivo depletion of MΦ, via clodronate-liposomes, suggest that
CD300f-expression on MΦ contributed to the protection against Rickettsia-induced lethality. Hence, we will test
the hypothesis, that both SFG and TGs Rickettsia exploit efferocytic signaling to invade MΦ, using the following
Aims: to identify rickettsial outer membrane glycerophospholipid [phosphatidylserine (PS) or other] ligand(s)
involved in the engulfment and colonization of pathogenic Rickettsia by MΦ (Aim 1) and define the contributing
role of glycerophospholipid-binding receptor, CD300f, in promoting engulfment and colonization of the host by
pathogenic Rickettsia in MΦ...

## Key facts

- **NIH application ID:** 10526450
- **Project number:** 1R21AI166821-01A1
- **Recipient organization:** UNIVERSITY OF MARYLAND BALTIMORE
- **Principal Investigator:** Mohammed Sayeedur Rahman
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $231,750
- **Award type:** 1
- **Project period:** 2022-08-01 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10526450

## Citation

> US National Institutes of Health, RePORTER application 10526450, Virulent Rickettsia species utilize the CD300f phosphatidylserine-binding receptor on macrophages for host colonization and pathogenesis (1R21AI166821-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10526450. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*